734:, the German Federal Agency for Sera and Vaccines, reviewed Germany's regulatory requirements in the aftermath of the TGN1412 trial. They suggested that the predictive value of pre-clinical animal models required reevaluation, dose fixing needed refinement or redesign, and criteria for high-risk antibodies needed to be established. Additionally, they suggested that pre-Phase I studies were needed to calculate a dose with a pre-clinical "No effect" level, rather than a
830:," but that "this information was given to the men and submitted to the test regulators." TeGenero said this was transient and was evidence of the extra T cells that the drug produces. Experiments with another drug affecting the CD28 receptor (but to a lesser extent than TGN1412) had also shown side effects in human trials. There have been criticisms that the risks taken and the design of the protocol were insufficiently justified by proper
517:, including the constant (Fc) region. According to a report by TeGenero, the F(ab)2 is not able to generate the required stimulation. Unlike the related clone TGN1112, an IgG1, TGN1412 is of the subclass IgG4. This choice was made as TGN1112 showed antibody-dependent cellular cytotoxicity on CD28+ Jurkat cells. Thus the function of antibody binding via an Fcγ receptor seems to be a requirement for the immune regulation. However, cell
746:. Animals raised in a sterile lab would presumably have no 'memory' of previous illnesses, thus would not exhibit the severe reactions that occurred in the human subjects. However this is a misunderstanding of the research: the research says that lab animals studied have fewer memory T cells than humans, and that stimulation through the CD28 receptor alone in memory T cells causes them to infiltrate organs and also activates them.
433:
345:
1646:
451:(signal 2). Studies of monoclonal antibodies specific for mouse, rat, or human CD28 identified so-called "superagonistic" antibodies that could stimulate T cells without concurrent antigen-receptor stimulation (signal 1). Whether this activity represents a stronger activity or a different activity is uncertain.
696:
appeared in order, including dose measurement and administration, and no deficiencies were found that may have led to contamination or overdose. The MHRA felt that their actions did not contribute to the serious adverse events. German regulatory authorities inspected the production of the material by
563:, on 13 March 2006. Parexel is a company that carries out drug trials on behalf of pharmaceutical and biotechnology companies. Healthy volunteers were recruited to the study with a £2,000 fee. The trial resulted in hospitalization of all six volunteers administered the drug, at least four of whom had
405:
of 5.11A1 were cloned into the framework of human IgG and combined with IgG1 (TGN1112) or IgG4 (TGN1412) constant regions. According to the company's
Investigator Brochure, "TGN1412 is a humanised monoclonal antibody directed against the human CD28 antigen. The molecule was genetically engineered by
825:
and who wished to remain anonymous said "You don't need to be a rocket scientist to work out what will happen if you non-specifically activate every T cell in the body." While the drug had appeared to be safe in animal models, researchers noted that there were reasons why these may not be indicative
587:
am, with an interval of around 10 minutes between patients, and each infusion lasting from 3 to 6 minutes. Roughly fifty minutes after the first participant received his dose, he complained of a headache, and soon afterwards fever and pain. He took his shirt off, complaining that he felt like he was
397:
Mice of the inbred strain BALB/c were immunized with recombinant human CD28-Fc fusion proteins and boosted with a B lymphoma cell line transfected to express human CD28. Hybridomas were obtained by fusing B cells with the hybridoma partner X63Ag8.653 and screened for reactivity with human CD28 and
718:
In
December 2006, the final report of the Expert Group on Phase One Clinical Trials was published. It found that the trial had not considered what constituted a safe dose in humans, and that then-current law had not required it. It made 22 recommendations, including the need for independent expert
695:
The
Medicines and Healthcare products Regulatory Agency (MHRA) issued an interim report on the TGN1412 trial on 5 April 2006, followed by a final report on 25 May 2006. It found no deficiencies in TeGenero's pre-clinical work and no evidence of undisclosed studies. Parexel's records and processes
454:
Two antibodies specific for human CD28 were identified. The more active of the two, TGN1112 (originally called 5.11A1), belonged to the IgG1 class of immunoglobulins. The other, TGN1412 (clone 9D7), belonged to the IgG4 class. The TCR-independent agonism of these antibodies involved binding to a
682:
TeGenero apologised to the families involved soon after the events, insisting that the effects were completely unexpected, and that all protocols were followed. In an initial review of pre-clinical data and the protocol, the MHRA stated there was nothing to cause concern, and that the trial was
541:, it caused catastrophic systemic organ failures in the subjects, despite being administered at a supposed sub-clinical dose of 0.1 mg per kg, some 500 times lower than the dose found safe in animals. Six volunteers were hospitalized on 13 March 2006. At least four of them had
412:] antibody (5.11A1, Luhder et al., 2003) into human heavy and light chain variable frameworks. Humanised variable regions were subsequently recombined with a human gene coding for the IgG4 gamma chain and with a human gene coding for a human kappa chain, respectively."
837:
Critics of animal testing have cited the case to argue that experiments on nonhuman animals, even in species closely related to humans, are not necessarily predictive of human responses, and cannot justify the harm inflicted on animals or the resultant risks to humans.
741:
Scientists in early 2007 put forth the theory that the drug acted in a different fashion in humans as compared with the laboratory animals in which the drug was first tried. The severe reactions in humans could have only occurred, they believe, in those with
715:, as Chair of the group. Until the expert group reported, all further clinical trial applications involving first-in-humans trials of any monoclonal antibody or other novel molecules targeting the immune system were not to be authorised in the UK.
675:
592:
12 hours after infusion, with the others following within the next 4 hours. A severely affected volunteer, Mohammed
Abdalla, a 28-year-old, was described as having developed a ballooned head. This led to his description as being similar to the
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TGN1412 was created to perfectly fit inside the CD28 receptor of humans. Animal trials on mice were not necessarily predictive of human responses, as it would require a much greater dosage to get the same level of immunoactivity as in a human.
494:
found that all T cells that get activated using conventional TCR-mediated stimulation become regulatory for a brief time and express FOXP3. However, eventually most of these cells downregulate their regulatory capabilities and become
753:
research and modelling, published in 2008, suggested that the 0.1 mg starting dose would bind to 86 to 91% of all CD28 receptors in the body, resulting in a possible higher than expected effect even at very low starting doses.
719:
advice before a high-risk study was allowed, testing only one volunteer at a time (sequential inclusion of participants) in case there were rapid ill effects, and administering drugs slowly by infusion rather than as an injection.
475:, leading to a net effect of T-cell downregulation. On its website, the company wrote: "A pronounced T-cell activation and expansion mediated by CD28-SuperMAB in animal models is accompanied by the expression of anti-inflammatory
666:
a profound activation of T cells, without clinically visible side effects" and goes on to say "This antibody—in spite of its strong T cell-stimulatory properties—is very well tolerated in vivo, in contrast to all other known
1899:
Liedert B, Bassus S, Schneider CK, Kalinke U, Löwer J (January 2007). "Safety of phase I clinical trials with monoclonal antibodies in
Germany--the regulatory requirements viewed in the aftermath of the TGN1412 disaster".
1813:
588:
burning. Shortly after, the remaining participants who received the actual drug also became ill, vomiting and complaining of severe pain. The first patient was transferred to the
Northwick Park Hospital's
761:
wrote that a near-maximum immuno-stimulatory dose had been given, because a safe starting dose in man had been calculated "based upon results from pre-clinical safety testing in a non-responsive species"
651:, where the men were treated, the patients continued to improve and "five of them went home within a month of the incident, while one patient remained in hospital until 26 June, when he also went home".
579:. All six of the trial subjects who received the drug were male, aged 19 to 34 (median 29.5); none had a notable medical history, and all were well in the 2 weeks before the trial. The drug was given by
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1408:
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agreed to establish a group of leading international experts to consider those issues and to provide a report on the future authorization of such trials with an interim report at three months, with
658:. The company claims that these did not indicate any safety issues, and this was supported in subsequent MHRA reports. The US patent application states "it could be shown in a pilot study that an
2271:
1644:, Thomas Hanke & Chia-Huey Lin, "Use of a CD28 binding pharmaceutical substance for making a pharmaceutical composition with dose-dependent effect", published 2006-01-12
483:
of pro-inflammatory mediators induced by other agents that address the TCR complex.". As it turned out, the results of the first trial in humans indicate that this may not always be the case.
1832:
455:
specific part of the CD28 molecule called the C"D loop. It was initially hypothesized that an antibody with this property could be therapeutically useful in stimulating the immune system in
800:
are not predictive of the unusual pro-inflammatory response to TGN1412, and gave a false negative result. IL-2 release and lymphoproliferation are more helpful predictors of the response.
2581:
758:
105:
700:, looking at the manufacture, testing, storage and distribution of the TGN1412, but no deficiencies were identified which could have contributed to the serious adverse effects.
1136:"TeGenero AG receives EU-orphan drug designation for Humanized Agonistic Anti-CD28 Monoclonal Antibody TGN1412 for the treatment of B-cell Chronic Lymphocytic Leukaemia, B-CLL"
1312:"Expression of CD28 and CD86 by human eosinophils and role in the secretion of type 1 cytokines (interleukin 2 and interferon gamma): inhibition by immunoglobulin a complexes"
826:
of the response in humans, particularly with respect to this type of drug. The BBC reported that "two of 20 monkeys used in earlier tests suffered an increase in the size of
436:
T lymphocyte activation pathway is triggered when a T cell encounters its cognate antigen, coupled to an MHC molecule, on the surface of an infected cell or a phagocyte.
331:. TeGenero announced the first elucidation of the molecular structure of CD28 almost exactly one year prior to commencement of the TGN1412 phase I clinical trial.
683:
correctly authorised. Participants who were harmed in the drug trial received some additional financial compensation later, which one participant used to hire a
1053:"Safety, Tolerability, Pharmacodynamics and Efficacy Study of TAB08 in Patients With Rheumatoid Arthritis in Which Methotrexate (MTX) Treatment is Not Effective"
398:
TCR-independent mitogenic activity. Two monoclonals called 5.11A1 and 9D7 were identified. The more active of the two, 5.11A1, is a mouse IgG1 immunoglobulin.
406:
transfer of the complementarity determining regions (CDRs) from heavy and light chain variable region sequences of a monoclonal mouse anti-humanC28 [
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1412:
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556:
47:
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The MHRA concluded that the most likely cause of the reaction in trial subjects was an unpredicted biological action of the drug in humans. The UK
274:. The drug was renamed TAB08. Phase I and II clinical trials have been completed for arthritis and clinical trials have been initiated for cancer.
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2245:
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785:, the species of primate used for pre-clinical safety testing of TGN1412, lack CD28 expression. Since CD28 is the target of the TGN1412 antibody,
308:. CD28 is the co-receptor for the T cell receptor; It binds to receptors on the interacting partner in the reaction through one of its ligands (
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2384:
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Lin CH, Kerkau T, Guntermann C, Trischler M, Beyersdorf N, Scheuring Y, Tony HP, Kneitz C, Wilhelm M, Mueller P, Huenig T (16 November 2004).
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Critics argued that the company should have anticipated that the drug would provoke a severe reaction in humans. An immunologist contacted by
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1110:"Superagonistic Anti-CD28 Antibody TGN1412 as a Potential Immunotherapeutic for the Treatment of B Cell Chronic Lymphocytic Leukemia"
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2327:
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384:
996:
1428:"CD4 depletion in HIV-infected haemophilia patients is associated with rapid clearance of immune complex-coated CD4+ lymphocytes"
735:
1936:
2089:"Monoclonal antibody TGN1412 trial failure explained by species differences in CD28 expression on CD4+ effector memory T-cells"
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experiments are limited to the use of purified peripheral blood mononuclear cells (PBMN's) that do not contain those cells.
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246:. It was withdrawn from development after inducing severe inflammatory reactions as well as chronic organ failure in the
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281:
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1852:"Transvaginal injection of potassium chloride and methotrexate for the treatment of tubal pregnancy with a live fetus"
549:
247:
1528:"Media Advisory: PAREXEL International Statement Regarding TeGenero AG Phase I Trial at Northwick Park Hospital, UK"
768:). It reported that the European guidelines for first-in-man phase-I clinical trials of biologics had been revised.
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270:(CEO) Benedikte Hatz went bankrupt later that year. The commercial rights were then acquired by a Russian startup,
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TGN1412 had not previously been given to humans, however the trial was preceded by animal testing, including in
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263:
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Suntharalingam G, Perry MR, Ward S, Brett SJ, Castello-Cortes A, Brunner MD, Panoskaltsis N (September 2006).
644:, involved in immune responses) had vanished almost completely several hours after administration of TGN1412.
2185:
Weißmüller S, Kronhart S, Kreuz D, Schnierle B, Kalinke U, Kirberg J, Hanschmann KM, Waibler Z (March 2016).
499:. Thus, attempts to induce FOXP3+ T cells might also induce effector cells capable of causing tissue damage.
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3595:
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1214:"Topological requirements and signaling properties of T cell-activating, anti-CD28 antibody superagonists"
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811:, destruction of white blood cells, and other negative effects observed during the initial human trial.
2011:
Waibler Z, Sender LY, Kamp C, Müller-Berghaus J, Liedert B, Schneider CK, et al. (November 2008).
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data from animal studies later suggested that administration would lead to preferential activation of
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2198:
1964:"Physiologic and aberrant regulation of memory T-cell trafficking by the costimulatory molecule CD28"
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1166:
712:
697:
580:
328:
285:
2052:
Stebbings R, Poole S, Thorpe R (December 2009). "Safety of biologics, lessons learnt from TGN1412".
555:
were conducted by
Parexel at an independent clinical trials unit in leased space on the premises of
1121:
951:"The rise and fall of the CD 28 superagonist TGN 1412 and its return as TAB 08: a personal account"
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2485:"When a Drug Trial Goes Wrong: Emergency at the Hospital (Medical Documentary) - Real Stories"
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to attempt to remove TGN1412 from their circulation. Paradoxically, some kinds of the men's
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Lühder F, Huang Y, Dennehy KM, Guntermann C, Müller I, Winkler E, et al. (April 2003).
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597:". A volunteer also lost his fingers and toes as a result of being injected with the drug.
156:
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1160:"Boehringer Ingelheim and TeGenero sign agreement to develop and manufacture CD28-SuperMAB"
1028:"Exclusive: Drug that caused 'elephant man' side effect makes comeback after 2006 disaster"
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1595:"Latest condition of patients following drug trial at independent PAREXEL research unit"
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Eastwood D, Findlay L, Poole S, Bird C, Wadhwa M, Moore M, et al. (October 2010).
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1597:(Press release). The North West London Hospitals NHS Trust. 5 July 2006. Archived from
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Daniel V, Melk A, Süsal C, Weimer R, Zimmermann R, Huth-Kühne A, Opelz G (March 1999).
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301:
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Duff GW, et al. (Expert Group on Phase One
Clinical Trials) (7 December 2006).
1394:
1359:
Woerly G, Lacy P, Younes AB, Roger N, Loiseau S, Moqbel R, Capron M (October 2002).
1185:"Investigator's Brochure. TGN1412 Humanized Agonistic Anti-CD28 Monoclonal Antibody"
807:
evaluated TGN1412's effects on the immune system, and confirmed that it could cause
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2187:"TGN1412 Induces Lymphopenia and Human Cytokine Release in a Humanized Mouse Model"
1997:
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518:
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A new explanation for the trial mishap was suggested by the findings of a paper in
575:, and six receiving 1/500th of the highest dose used in previous experiments with
513:
To function as an agonist, it has been suggested that TGN1412 needs to be a whole
2211:
2153:
2065:
1980:
1962:
Mirenda V, Jarmin SJ, David R, Dyson J, Scott D, Gu Y, et al. (April 2007).
1361:"Human eosinophils express and release IL-13 following CD28-dependent activation"
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1488:"Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412"
877:
708:
496:
432:
344:
316:
98:
2029:
2012:
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1278:
1263:"Transient regulatory T-cells: a state attained by all activated human T-cells"
262:
of the
University of Würzburg around immunologist Thomas Hünig, co-founder and
254:
in London in March 2006. The developing company, TeGenero Immuno
Therapeutics (
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Woerly G, Roger N, Loiseau S, Dombrowicz D, Capron A, Capron M (August 1999).
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Nature news: Animal tests may have missed danger because monkeys 'too clean'
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Medicines and Healthcare Products Regulatory Agency (MHRA) (25 May 2006).
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2013:"Toward experimental assessment of receptor occupancy: TGN1412 revisited"
1814:"Investigations Into Adverse Incidents During Clinical Trials of TGN1412"
1504:
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1409:"Investigations into adverse incidents during clinical trials of TGN1412"
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369: in this section. Unsourced material may be challenged and removed.
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1194:. Citizens For Responsible Care and Research (CIRCARE). Archived from
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administration of anti-human CD28-SuperMAB induces in a rhesus monkey
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Working Party on Statistical Issues in First-in-Man Studies (2007).
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The human clinical trial of TGN1412 was the subject of the 2017 BBC
673:
431:
66:
792:
In 2013, it was described that standard pro-inflammatory markers
419:
and the recombinant antibody harvested from culture supernatant.
2246:"Catastrophic immune response may have caused drug trial horror"
1765:"Germany may change drug testing rules after debacle in England"
609:
297:
79:
2563:
2138:"After TGN1412: recent developments in cytokine release assays"
1902:
International Journal of Clinical Pharmacology and Therapeutics
727:
The trial has become subject of several academic publications.
506:. They can release IFN-γ, IL-2, IL-4, and IL-13. However, most
775:
in humans was explained. In vitro data revealed that the CD4+
526:
408:
338:
1707:"Press release: Latest findings on clinical trial suspension"
2543:
crisis communications case study of Tegenero clinical trial
1165:(Press release). TeGenero. 17 November 2003. Archived from
1261:
Pillai V, Ortega SB, Wang CK, Karandikar NJ (April 2007).
2328:"Update to frequently asked questions regarding TGN1412"
1141:(Press release). TeGenero. 13 March 2005. Archived from
600:
All of the men were reported to have experienced severe
1833:
Expert Group on Phase One Clinical Trials: Final report
1530:(Press release). PAREXEL. 13 March 2006. Archived from
759:
National Institute for Biological Standards and Control
206:
789:
effector T-cells could not be stimulated by the drug.
2460:"BBC Two - The Drug Trial: Emergency at the Hospital"
2412:"The flaws and human harms of animal experimentation"
502:
Other cells activated by CD28 ligation in humans are
1850:
Aboulghar MA, Mansour RT, Serour GI (October 1990).
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in March 2005, was developed by TeGenero, tested by
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2136:Stebbings R, Eastwood D, Poole S, Thorpe R (2013).
1617:"Data for botched drugs trial show 'nothing' amiss"
1059:. US National Library of Medicine. 27 February 2017
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not approved by any regulatory agency, highly toxic
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928:. London: Fourth Estate. pp. 8–10, 104–105.
647:According to a press release on 5 July 2006 from
1835:(Report). The Stationery Office. Archived from
1610:
1608:
155:
2359:"Tragic drug trial spotlights potent molecule"
2017:The Journal of Allergy and Clinical Immunology
2575:
571:, with two of the eight subjects receiving a
525:of the labeled cells, as seen in the case of
8:
2385:"Statistical issues in first-in-man studies"
2272:"Antibody 'puts immune system in overdrive'"
1581:"Would you accept £3,750 to trial one drug?"
567:. The trial was a double-blind, randomized,
415:The recombinant genes were transfected into
32:
2523:BBC News: Drug trial man 'may lose fingers'
2244:Bhattacharya S, Coghlan A (17 March 2006).
3547:
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1937:"Study claims to solve drug trial mystery"
2533:Channel 4: The Drug Trial That Went Wrong
2528:BBC News: Regulators slam drug trial firm
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1979:
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1681:"'I nearly died in a medical drug trial'"
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850:The Drug Trial: Emergency at the Hospital
771:In 2010, the failure to predict a severe
443:normally requires both engagement of the
385:Learn how and when to remove this message
277:Originally intended for the treatment of
191:
2555:Further lessons from the TGN1412 tragedy
2416:Cambridge Quarterly of Healthcare Ethics
2389:Journal of the Royal Statistical Society
479:, like IL-10, rather than by the severe
292:that not only binds to, but is a strong
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1662:"Drug trial leaves men critically ill"
557:Northwick Park and St. Mark's Hospital
31:
2495:from the original on 22 December 2021
711:, Professor of Molecular Medicine at
687:so he could regain physical fitness.
649:North West London Hospitals NHS Trust
315:The drug, which was designated as an
7:
1615:Urquhart L, Jack A (16 March 2006).
1432:Clinical and Experimental Immunology
1316:The Journal of Experimental Medicine
1218:The Journal of Experimental Medicine
1114:Blood (ASH Annual Meeting Abstracts)
916:
914:
367:adding citations to reliable sources
2302:"Trial drug affected animal glands"
1492:The New England Journal of Medicine
1120:(11): Abstract 2519. Archived from
403:complementarity-determining regions
3655:Experimental monoclonal antibodies
25:
1554:"Drugs trial men 'are improving'"
624:. The patients were treated with
2105:10.1111/j.1476-5381.2010.00922.x
2054:Current Opinion in Biotechnology
1679:Caffrey, Jason (19 March 2016).
1444:10.1046/j.1365-2249.1999.00848.x
1183:TeGenero AG (19 December 2005).
803:In 2016, a study carried out on
736:No-observed-adverse-effect level
730:In 2007, immunologists from the
343:
2334:. 19 March 2006. Archived from
2093:British Journal of Pharmacology
1713:(Press release). Archived from
354:needs additional citations for
3635:Drugs not assigned an ATC code
521:by antibody leads normally to
1:
1738:"Clinical trial final report"
1081:TeGenero (20 February 2006).
1026:Hirschler B (24 March 2015).
949:Hünig, Thomas (18 May 2016).
705:Secretary of State for Health
616:, akin to the effects of the
290:humanised monoclonal antibody
2212:10.1371/journal.pone.0149093
2154:10.3109/1547691X.2012.711783
2066:10.1016/j.copbio.2009.10.002
1981:10.1182/blood-2006-10-050724
1579:Palmer K (15 October 2014).
1365:Journal of Leukocyte Biology
628:to reduce inflammation, and
282:chronic lymphocytic leukemia
2518:Report in Nature on TGN1412
2357:Pearson H (17 March 2006).
2142:Journal of Immunotoxicology
1935:Fleming N (12 April 2008).
1868:10.1136/bmj.39062.336157.DB
417:Chinese hamster ovary cells
3676:
2030:10.1016/j.jaci.2008.07.049
1781:10.1136/bmj.332.7544.746-c
1660:Weaver M (15 March 2006).
1279:10.1016/j.clim.2006.10.014
1085:. TeGenero. Archived from
565:multiple organ dysfunction
543:multiple organ dysfunction
3585:
2428:10.1017/S0963180115000079
2410:Akhtar A (October 2015).
2395:: 517–579. Archived from
863:Adverse effect (medicine)
809:cytokine release syndrome
773:cytokine release syndrome
602:cytokine release syndrome
481:cytokine release syndrome
321:European Medicines Agency
202:
3645:Clinical trial disasters
2278:. London. Archived from
2270:Hall C (17 March 2006).
893:Pre-clinical development
671:activating substances."
622:severe allergic reaction
569:placebo-controlled study
264:chief scientific officer
868:Clinical trial protocol
777:effector memory T-cells
678:Structure of human CD28
504:eosinophil granulocytes
268:chief executive officer
266:(CSO) Thomas Hanke and
1763:Tuffs A (April 2006).
1740:. MHRA. Archived from
1411:. MHRA. Archived from
732:Paul Ehrlich Institute
723:Follow up publications
679:
437:
317:orphan medical product
244:University of Würzburg
3640:Monoclonal antibodies
2669:Camidanlumab tesirine
2591:Monoclonal antibodies
1812:MHRA (5 April 2006).
1705:MHRA (5 April 2006).
1328:10.1084/jem.190.4.487
677:
441:Activation of T cells
435:
3344:Chimeric + humanized
2873:Nivolumab/relatlimab
2548:9 March 2009 at the
1601:on 7 September 2012.
1505:10.1056/NEJMoa063842
1378:10.1189/jlb.72.4.769
1230:10.1084/jem.20021024
1001:The Org (theorg.com)
832:statistical evidence
744:memory T lymphocytes
713:Sheffield University
698:Boehringer Ingelheim
581:intravenous infusion
363:improve this article
329:Boehringer Ingelheim
327:and manufactured by
286:rheumatoid arthritis
248:first-in-human study
2276:The Daily Telegraph
2203:2016PLoSO..1149093W
1941:The Daily Telegraph
1267:Clinical Immunology
782:Macaca fascicularis
765:Macaca fascicularis
590:intensive care unit
577:cynomolgus macaques
537:In its first human
488:Clinical Immunology
459:patients. However,
428:Mechanism of action
41:Monoclonal antibody
36:
27:Monoclonal antibody
3612:Never to phase III
3058:Certolizumab pegol
3025:Immunosuppressive:
2399:on 5 January 2012.
1856:Human Reproduction
1839:on 7 January 2013.
1744:on 6 December 2014
1717:on 5 December 2014
1415:on 21 August 2007.
1083:"Drug Development"
1057:ClinicalTrials.gov
967:10.1111/febs.13754
680:
656:non-human primates
618:complement cascade
473:regulatory T cells
438:
235:drug developed by
3622:
3621:
3581:
3580:
3536:
3535:
3370:
3369:
3325:Immune activation
2817:Immune activation
2619:Immunosuppression
1498:(10): 1018–1028.
1172:on 18 March 2006.
1148:on 19 March 2006.
1124:on 14 April 2013.
1007:on 25 August 2024
961:(18): 3325–3334.
873:Pharmacovigilance
634:white blood cells
395:
394:
387:
214:
213:
16:(Redirected from
3667:
3548:
3381:
2939:Zolimomab aritox
2929:Telimomab aritox
2608:
2584:
2577:
2570:
2561:
2505:
2504:
2502:
2500:
2481:
2475:
2474:
2472:
2470:
2456:
2450:
2449:
2439:
2407:
2401:
2400:
2380:
2374:
2373:
2371:
2369:
2354:
2348:
2347:
2345:
2343:
2324:
2318:
2317:
2315:
2313:
2298:
2292:
2291:
2289:
2287:
2267:
2261:
2260:
2258:
2256:
2241:
2235:
2234:
2224:
2214:
2182:
2176:
2175:
2165:
2133:
2127:
2126:
2116:
2084:
2078:
2077:
2049:
2043:
2042:
2032:
2008:
2002:
2001:
1983:
1959:
1953:
1952:
1950:
1948:
1932:
1926:
1925:
1914:10.5414/CPP45001
1896:
1890:
1889:
1879:
1847:
1841:
1840:
1828:
1822:
1821:
1816:. Archived from
1809:
1803:
1802:
1792:
1760:
1754:
1753:
1751:
1749:
1733:
1727:
1726:
1724:
1722:
1702:
1696:
1695:
1693:
1691:
1676:
1670:
1669:
1657:
1651:
1650:
1649:
1645:
1638:
1632:
1631:
1629:
1627:
1612:
1603:
1602:
1591:
1585:
1584:
1576:
1570:
1569:
1567:
1565:
1550:
1544:
1543:
1541:
1539:
1524:
1518:
1517:
1507:
1483:
1466:
1465:
1455:
1423:
1417:
1416:
1405:
1399:
1398:
1380:
1356:
1350:
1349:
1339:
1307:
1301:
1300:
1290:
1258:
1252:
1251:
1241:
1209:
1203:
1202:
1201:on 29 June 2006.
1200:
1189:
1180:
1174:
1173:
1171:
1164:
1156:
1150:
1149:
1147:
1140:
1132:
1126:
1125:
1105:
1099:
1098:
1096:
1094:
1089:on 12 April 2006
1078:
1069:
1068:
1066:
1064:
1049:
1043:
1042:
1040:
1038:
1023:
1017:
1016:
1014:
1012:
1003:. Archived from
993:
987:
986:
955:The FEBS Journal
946:
940:
939:
918:
888:Drug development
757:In 2009, the UK
685:personal trainer
614:mucous membranes
586:
457:immunosuppressed
445:antigen receptor
390:
383:
379:
376:
370:
347:
339:
300:receptor of the
233:immunomodulatory
210:
209:
195:
159:
37:
35:
21:
3675:
3674:
3670:
3669:
3668:
3666:
3665:
3664:
3660:Abandoned drugs
3625:
3624:
3623:
3618:
3617:
3602:Clinical trials
3577:
3532:
3516:
3445:
3366:
3357:Rozanolixizumab
3345:
3339:
3331:
3320:
3133:Lulizumab pegol
3011:
2943:
2877:
2597:
2588:
2550:Wayback Machine
2514:
2509:
2508:
2498:
2496:
2483:
2482:
2478:
2468:
2466:
2458:
2457:
2453:
2409:
2408:
2404:
2382:
2381:
2377:
2367:
2365:
2356:
2355:
2351:
2341:
2339:
2326:
2325:
2321:
2311:
2309:
2308:. 20 March 2006
2300:
2299:
2295:
2285:
2283:
2269:
2268:
2264:
2254:
2252:
2243:
2242:
2238:
2197:(3): e0149093.
2184:
2183:
2179:
2135:
2134:
2130:
2086:
2085:
2081:
2051:
2050:
2046:
2010:
2009:
2005:
1961:
1960:
1956:
1946:
1944:
1934:
1933:
1929:
1898:
1897:
1893:
1849:
1848:
1844:
1830:
1829:
1825:
1811:
1810:
1806:
1762:
1761:
1757:
1747:
1745:
1735:
1734:
1730:
1720:
1718:
1704:
1703:
1699:
1689:
1687:
1678:
1677:
1673:
1659:
1658:
1654:
1647:
1642:US 2006009382A1
1640:
1639:
1635:
1625:
1623:
1621:Financial Times
1614:
1613:
1606:
1593:
1592:
1588:
1578:
1577:
1573:
1563:
1561:
1560:. 18 March 2006
1552:
1551:
1547:
1537:
1535:
1526:
1525:
1521:
1485:
1484:
1469:
1425:
1424:
1420:
1407:
1406:
1402:
1358:
1357:
1353:
1309:
1308:
1304:
1260:
1259:
1255:
1211:
1210:
1206:
1198:
1187:
1182:
1181:
1177:
1169:
1162:
1158:
1157:
1153:
1145:
1138:
1134:
1133:
1129:
1107:
1106:
1102:
1092:
1090:
1080:
1079:
1072:
1062:
1060:
1051:
1050:
1046:
1036:
1034:
1025:
1024:
1020:
1010:
1008:
995:
994:
990:
948:
947:
943:
936:
920:
919:
912:
907:
902:
858:
817:
787:M. fascicularis
725:
693:
630:plasma-exchange
626:corticosteroids
584:
583:, starting at 8
553:clinical trials
539:clinical trials
535:
447:(signal 1) and
430:
425:
391:
380:
374:
371:
360:
348:
337:
288:, TGN1412 is a
219:(also known as
205:
203:
198:
178:
162:
137:
116:
93:
28:
23:
22:
15:
12:
11:
5:
3673:
3671:
3663:
3662:
3657:
3652:
3650:2006 in London
3647:
3642:
3637:
3627:
3626:
3620:
3619:
3616:
3615:
3614:
3613:
3610:
3599:
3593:
3587:
3586:
3583:
3582:
3579:
3578:
3576:
3575:
3570:
3565:
3560:
3554:
3552:
3545:
3538:
3537:
3534:
3533:
3531:
3530:
3524:
3522:
3518:
3517:
3515:
3514:
3509:
3504:
3499:
3494:
3489:
3484:
3479:
3474:
3469:
3464:
3459:
3453:
3451:
3447:
3446:
3444:
3443:
3438:
3433:
3428:
3423:
3418:
3413:
3408:
3403:
3398:
3393:
3387:
3385:
3378:
3372:
3371:
3368:
3367:
3365:
3364:
3359:
3354:
3348:
3346:
3341:
3340:
3322:
3321:
3315:
3310:
3305:
3300:
3295:
3290:
3285:
3280:
3275:
3270:
3265:
3260:
3255:
3250:
3245:
3240:
3235:
3230:
3225:
3220:
3215:
3210:
3205:
3200:
3195:
3190:
3185:
3180:
3175:
3170:
3165:
3160:
3157:+hyaluronidase
3150:
3145:
3140:
3135:
3130:
3125:
3120:
3115:
3110:
3105:
3100:
3095:
3090:
3085:
3080:
3075:
3070:
3065:
3060:
3055:
3050:
3045:
3040:
3035:
3030:
3021:
3019:
3013:
3012:
3010:
3009:
3004:
2999:
2994:
2989:
2984:
2979:
2974:
2969:
2964:
2959:
2953:
2951:
2945:
2944:
2942:
2941:
2936:
2931:
2926:
2921:
2916:
2911:
2906:
2901:
2896:
2891:
2885:
2883:
2879:
2878:
2876:
2875:
2865:
2864:
2859:
2854:
2844:
2843:
2838:
2833:
2828:
2823:
2813:
2812:
2807:
2802:
2797:
2792:
2787:
2782:
2777:
2772:
2767:
2761:
2756:
2751:
2746:
2741:
2736:
2731:
2726:
2721:
2716:
2711:
2706:
2701:
2696:
2691:
2686:
2681:
2676:
2671:
2666:
2661:
2656:
2651:
2646:
2641:
2636:
2631:
2626:
2614:
2612:
2605:
2599:
2598:
2589:
2587:
2586:
2579:
2572:
2564:
2558:
2557:
2552:
2540:
2535:
2530:
2525:
2520:
2513:
2512:External links
2510:
2507:
2506:
2476:
2451:
2402:
2375:
2349:
2338:on 21 May 2006
2319:
2293:
2282:on 18 May 2007
2262:
2236:
2177:
2128:
2079:
2044:
2003:
1974:(7): 2968–77.
1954:
1927:
1891:
1842:
1823:
1820:on 5 May 2011.
1804:
1755:
1728:
1697:
1671:
1652:
1633:
1604:
1586:
1571:
1545:
1534:on 13 May 2006
1519:
1467:
1418:
1400:
1351:
1302:
1253:
1204:
1175:
1151:
1127:
1100:
1070:
1044:
1018:
997:"Thomas Hanke"
988:
941:
934:
909:
908:
906:
903:
901:
900:
898:EudraVigilance
895:
890:
885:
883:Co-stimulation
880:
875:
870:
865:
859:
857:
854:
816:
813:
805:humanized mice
724:
721:
692:
691:Investigations
689:
608:, swelling of
534:
531:
497:effector cells
449:co-stimulation
429:
426:
424:
421:
393:
392:
351:
349:
342:
336:
333:
212:
211:
200:
199:
197:
196:
188:
186:
180:
179:
177:
176:
172:
170:
164:
163:
161:
160:
152:
150:
144:
143:
139:
138:
136:
135:
131:
129:
123:
122:
118:
117:
115:
114:
110:
108:
102:
101:
96:
94:administration
88:
87:
83:
82:
77:
71:
70:
60:
54:
53:
52:Whole antibody
50:
44:
43:
26:
24:
14:
13:
10:
9:
6:
4:
3:
2:
3672:
3661:
3658:
3656:
3653:
3651:
3648:
3646:
3643:
3641:
3638:
3636:
3633:
3632:
3630:
3611:
3609:
3606:
3605:
3603:
3600:
3597:
3594:
3592:
3589:
3588:
3584:
3574:
3571:
3569:
3566:
3564:
3561:
3559:
3556:
3555:
3553:
3549:
3546:
3544:
3541:Inflammatory
3539:
3529:
3526:
3525:
3523:
3519:
3513:
3512:Tildrakizumab
3510:
3508:
3505:
3503:
3500:
3498:
3495:
3493:
3490:
3488:
3485:
3483:
3480:
3478:
3475:
3473:
3470:
3468:
3465:
3463:
3460:
3458:
3455:
3454:
3452:
3448:
3442:
3439:
3437:
3434:
3432:
3429:
3427:
3424:
3422:
3419:
3417:
3414:
3412:
3409:
3407:
3404:
3402:
3399:
3397:
3394:
3392:
3389:
3388:
3386:
3382:
3379:
3377:
3373:
3363:
3360:
3358:
3355:
3353:
3350:
3349:
3347:
3342:
3338:
3337:
3334:
3330:
3326:
3319:
3316:
3314:
3313:Vobarilizumab
3311:
3309:
3306:
3304:
3301:
3299:
3296:
3294:
3291:
3289:
3286:
3284:
3281:
3279:
3276:
3274:
3271:
3269:
3266:
3264:
3261:
3259:
3258:Spartalizumab
3256:
3254:
3251:
3249:
3246:
3244:
3241:
3239:
3236:
3234:
3231:
3229:
3226:
3224:
3221:
3219:
3216:
3214:
3211:
3209:
3206:
3204:
3201:
3199:
3196:
3194:
3191:
3189:
3186:
3184:
3183:Pembrolizumab
3181:
3179:
3176:
3174:
3171:
3169:
3166:
3164:
3161:
3158:
3154:
3151:
3149:
3146:
3144:
3143:Mogamulizumab
3141:
3139:
3136:
3134:
3131:
3129:
3126:
3124:
3121:
3119:
3116:
3114:
3111:
3109:
3106:
3104:
3101:
3099:
3096:
3094:
3091:
3089:
3086:
3084:
3081:
3079:
3076:
3074:
3071:
3069:
3066:
3064:
3063:Crizanlizumab
3061:
3059:
3056:
3054:
3051:
3049:
3046:
3044:
3041:
3039:
3036:
3034:
3031:
3029:
3026:
3023:
3022:
3020:
3018:
3014:
3008:
3005:
3003:
3000:
2998:
2995:
2993:
2990:
2988:
2985:
2983:
2980:
2978:
2975:
2973:
2970:
2968:
2965:
2963:
2960:
2958:
2957:Andecaliximab
2955:
2954:
2952:
2950:
2946:
2940:
2937:
2935:
2932:
2930:
2927:
2925:
2922:
2920:
2917:
2915:
2912:
2910:
2907:
2905:
2902:
2900:
2897:
2895:
2892:
2890:
2887:
2886:
2884:
2880:
2874:
2870:
2867:
2866:
2863:
2860:
2858:
2855:
2853:
2849:
2846:
2845:
2842:
2839:
2837:
2834:
2832:
2829:
2827:
2824:
2822:
2818:
2815:
2814:
2811:
2808:
2806:
2803:
2801:
2798:
2796:
2793:
2791:
2788:
2786:
2783:
2781:
2778:
2776:
2773:
2771:
2768:
2765:
2762:
2760:
2757:
2755:
2752:
2750:
2747:
2745:
2742:
2740:
2737:
2735:
2732:
2730:
2727:
2725:
2722:
2720:
2717:
2715:
2712:
2710:
2707:
2705:
2702:
2700:
2697:
2695:
2692:
2690:
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2632:
2630:
2627:
2625:
2621:
2620:
2616:
2615:
2613:
2609:
2606:
2604:
2603:Immune system
2600:
2596:
2595:immune system
2592:
2585:
2580:
2578:
2573:
2571:
2566:
2565:
2562:
2556:
2553:
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2547:
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2539:
2536:
2534:
2531:
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2486:
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2477:
2465:
2461:
2455:
2452:
2447:
2443:
2438:
2433:
2429:
2425:
2422:(4): 407–19.
2421:
2417:
2413:
2406:
2403:
2398:
2394:
2390:
2386:
2379:
2376:
2364:
2360:
2353:
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2333:
2329:
2323:
2320:
2307:
2303:
2297:
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2281:
2277:
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2251:
2250:New Scientist
2247:
2240:
2237:
2232:
2228:
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2204:
2200:
2196:
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2178:
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2169:
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2147:
2143:
2139:
2132:
2129:
2124:
2120:
2115:
2110:
2106:
2102:
2099:(3): 512–26.
2098:
2094:
2090:
2083:
2080:
2075:
2071:
2067:
2063:
2059:
2055:
2048:
2045:
2040:
2036:
2031:
2026:
2022:
2018:
2014:
2007:
2004:
1999:
1995:
1991:
1987:
1982:
1977:
1973:
1969:
1965:
1958:
1955:
1942:
1938:
1931:
1928:
1923:
1919:
1915:
1911:
1907:
1903:
1895:
1892:
1887:
1883:
1878:
1873:
1869:
1865:
1861:
1857:
1853:
1846:
1843:
1838:
1834:
1827:
1824:
1819:
1815:
1808:
1805:
1800:
1796:
1791:
1786:
1782:
1778:
1775:(7544): 746.
1774:
1770:
1766:
1759:
1756:
1743:
1739:
1732:
1729:
1716:
1712:
1711:Press Release
1708:
1701:
1698:
1686:
1682:
1675:
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1667:
1663:
1656:
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1637:
1634:
1622:
1618:
1611:
1609:
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1600:
1596:
1590:
1587:
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1575:
1572:
1559:
1555:
1549:
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1533:
1529:
1523:
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1515:
1511:
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1501:
1497:
1493:
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1478:
1476:
1474:
1472:
1468:
1463:
1459:
1454:
1449:
1445:
1441:
1438:(3): 477–84.
1437:
1433:
1429:
1422:
1419:
1414:
1410:
1404:
1401:
1396:
1392:
1388:
1384:
1379:
1374:
1371:(4): 769–79.
1370:
1366:
1362:
1355:
1352:
1347:
1343:
1338:
1333:
1329:
1325:
1322:(4): 487–95.
1321:
1317:
1313:
1306:
1303:
1298:
1294:
1289:
1284:
1280:
1276:
1272:
1268:
1264:
1257:
1254:
1249:
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1240:
1235:
1231:
1227:
1224:(8): 955–66.
1223:
1219:
1215:
1208:
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1197:
1193:
1186:
1179:
1176:
1168:
1161:
1155:
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1128:
1123:
1119:
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1111:
1104:
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1088:
1084:
1077:
1075:
1071:
1058:
1054:
1048:
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1033:
1029:
1022:
1019:
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1002:
998:
992:
989:
984:
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976:
972:
968:
964:
960:
956:
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945:
942:
937:
935:9780007350742
931:
927:
923:
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904:
899:
896:
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869:
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861:
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853:
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848:
843:
839:
835:
833:
829:
824:
823:
822:New Scientist
815:Controversies
814:
812:
810:
806:
801:
799:
795:
790:
788:
784:
783:
778:
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769:
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749:Experimental
747:
745:
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733:
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623:
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604:resulting in
603:
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357:
352:This section
350:
346:
341:
340:
334:
332:
330:
326:
322:
318:
313:
311:
307:
303:
302:immune system
299:
295:
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280:
275:
273:
269:
265:
261:
257:
253:
249:
245:
241:
238:
234:
230:
226:
225:CD28-SuperMAB
222:
218:
208:
201:
194:
190:
189:
187:
185:
181:
174:
173:
171:
169:
165:
158:
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133:
132:
130:
128:
124:
119:
112:
111:
109:
107:
103:
100:
97:
95:
89:
86:Clinical data
84:
81:
78:
76:
72:
68:
64:
61:
59:
55:
51:
49:
45:
42:
38:
30:
19:
3502:Risankizumab
3487:Lebrikizumab
3467:Clazakizumab
3457:Anrukinzumab
3436:Tralokinumab
3352:Otelixizumab
3332:
3324:
3323:
3293:Tregalizumab
3278:Tislelizumab
3248:Satralizumab
3228:Rontalizumab
3223:Retifanlimab
3198:Plozalizumab
3178:Pateclizumab
3173:Pascolizumab
3168:Ozoralizumab
3118:Lampalizumab
3108:Inebilizumab
3098:Fontolizumab
3048:Camrelizumab
3043:Benralizumab
3038:Atezolizumab
3024:
2967:Clenoliximab
2868:
2852:Bertilimumab
2847:
2836:Tremelimumab
2816:
2739:Mavrilimumab
2729:Lirentelimab
2724:Lerdelimumab
2699:Fresolimumab
2639:Atorolimumab
2617:
2497:. Retrieved
2488:
2479:
2467:. Retrieved
2463:
2454:
2419:
2415:
2405:
2397:the original
2392:
2388:
2378:
2366:. Retrieved
2362:
2352:
2340:. Retrieved
2336:the original
2331:
2322:
2310:. Retrieved
2305:
2296:
2284:. Retrieved
2280:the original
2275:
2265:
2253:. Retrieved
2249:
2239:
2194:
2190:
2180:
2148:(1): 75–82.
2145:
2141:
2131:
2096:
2092:
2082:
2060:(6): 673–7.
2057:
2053:
2047:
2023:(5): 890–2.
2020:
2016:
2006:
1971:
1967:
1957:
1945:. Retrieved
1940:
1930:
1905:
1901:
1894:
1862:(7): 887–8.
1859:
1855:
1845:
1837:the original
1826:
1818:the original
1807:
1772:
1768:
1758:
1746:. Retrieved
1742:the original
1731:
1719:. Retrieved
1715:the original
1710:
1700:
1688:. Retrieved
1684:
1674:
1666:The Guardian
1665:
1655:
1636:
1624:. Retrieved
1620:
1599:the original
1589:
1574:
1562:. Retrieved
1557:
1548:
1536:. Retrieved
1532:the original
1522:
1495:
1491:
1435:
1431:
1421:
1413:the original
1403:
1368:
1364:
1354:
1319:
1315:
1305:
1273:(1): 18–29.
1270:
1266:
1256:
1221:
1217:
1207:
1196:the original
1191:
1178:
1167:the original
1154:
1143:the original
1130:
1122:the original
1117:
1113:
1103:
1091:. Retrieved
1087:the original
1061:. Retrieved
1056:
1047:
1035:. Retrieved
1031:
1021:
1009:. Retrieved
1005:the original
1000:
991:
958:
954:
944:
925:
849:
844:
840:
836:
820:
818:
802:
791:
786:
780:
770:
763:
756:
748:
740:
729:
726:
717:
702:
694:
681:
653:
646:
599:
595:Elephant Man
547:
536:
523:phagocytosis
519:opsonisation
512:
507:
501:
491:
487:
485:
466:
460:
453:
439:
423:Pharmacology
414:
407:
400:
396:
381:
372:
361:Please help
356:verification
353:
314:
284:(B-CLL) and
276:
240:Thomas Hünig
237:immunologist
228:
224:
220:
217:Theralizumab
216:
215:
204:
127:Legal status
121:Legal status
34:Theralizumab
29:
3598:from market
3568:Lemalesomab
3563:Fanolesomab
3558:Besilesomab
3497:Perakizumab
3482:Mirikizumab
3472:Gevokizumab
3462:Bimekizumab
3441:Ustekinumab
3426:Secukinumab
3411:Fezakinumab
3406:Canakinumab
3401:Briakinumab
3376:Interleukin
3329:Dostarlimab
3308:Visilizumab
3303:Vedolizumab
3298:Vatelizumab
3288:Toralizumab
3283:Tocilizumab
3268:Teclistamab
3243:Samalizumab
3233:Rovelizumab
3213:Ravulizumab
3193:Pidilizumab
3188:Pexelizumab
3153:Ocrelizumab
3148:Natalizumab
3138:Mepolizumab
3128:Ligelizumab
3123:Letolizumab
3093:Etrolizumab
3083:Epratuzumab
3053:Cedelizumab
3007:Vapaliximab
3002:Teneliximab
2992:Lumiliximab
2977:Gomiliximab
2962:Basiliximab
2934:Vepalimomab
2919:Nerelimomab
2904:Gavilimomab
2899:Faralimomab
2894:Elsilimomab
2869:Combination
2862:Zanolimumab
2857:Ontamalimab
2805:Ulocuplumab
2800:Tezepelumab
2790:Sifalimumab
2770:Pamrevlumab
2749:Morolimumab
2744:Metelimumab
2714:Lanadelumab
2649:Avdoralimab
2634:Anifrolumab
2469:24 December
1748:29 November
1192:circare.org
1037:26 November
878:BIA 10-2474
828:lymph nodes
709:Gordon Duff
638:lymphocytes
157:906068-56-2
142:Identifiers
99:intravenous
3629:Categories
3528:Lokivetmab
3521:Veterinary
3507:Spesolimab
3492:Olokizumab
3477:Ixekizumab
3421:Guselkumab
3416:Fletikumab
3396:Brazikumab
3391:Bermekimab
3362:Sutimlimab
3336:Ibalizumab
3273:Teplizumab
3253:Siplizumab
3238:Ruplizumab
3218:Reslizumab
3208:Quilizumab
3163:Omalizumab
3113:Itolizumab
3103:Frexalimab
3078:Efalizumab
3073:Eculizumab
3068:Daclizumab
3033:Aselizumab
3028:Apolizumab
2997:Priliximab
2982:Infliximab
2924:Odulimomab
2914:Maslimomab
2909:Inolimomab
2889:Afelimomab
2826:Durvalumab
2821:Ipilimumab
2810:Varlilumab
2780:Relatlimab
2775:Placulumab
2719:Lenzilumab
2694:Emapalumab
2679:Cemiplimab
2664:Brodalumab
2659:Bleselumab
2629:Adalimumab
1908:(1): 1–9.
1690:28 October
926:Bad Pharma
922:Goldacre B
905:References
606:angioedema
335:Production
193:POO0DOD3AS
168:ChemSpider
148:CAS Number
3608:Phase III
3596:Withdrawn
3573:Sulesomab
3450:Humanized
3431:Sirukumab
3263:Talizumab
3088:Erlizumab
3017:Humanized
2987:Keliximab
2972:Galiximab
2831:Nivolumab
2795:Tabalumab
2785:Sarilumab
2759:Oleclumab
2754:Namilumab
2734:Lirilumab
2709:Ianalumab
2704:Golimumab
2689:Eldelumab
2684:Dupilumab
2654:Belimumab
2624:Abrilumab
1011:25 August
975:1742-464X
847:docudrama
642:monocytes
490:. Pillai
477:cytokines
375:July 2021
310:B7 family
296:for, the
92:Routes of
63:Humanized
2949:Chimeric
2841:Urelumab
2764:Oxelumab
2674:Carlumab
2644:Avelumab
2593:for the
2546:Archived
2499:24 March
2493:Archived
2446:26364776
2368:19 March
2342:20 March
2332:TeGenero
2312:20 March
2306:BBC News
2286:19 March
2255:19 March
2231:26959227
2191:PLOS ONE
2172:22967038
2123:20880392
2074:19892543
2039:18805577
1990:17119120
1943:. London
1922:17256444
1799:16575061
1685:BBC News
1626:17 March
1564:18 March
1558:BBC News
1538:15 March
1514:16908486
1462:10193421
1395:10820672
1387:12377947
1346:10449520
1297:17185041
1248:12707299
1093:16 March
983:27191544
924:(2012).
856:See also
751:in-vitro
660:in vitro
515:antibody
508:in vitro
462:in vitro
272:TheraMAB
260:spin-off
256:TeGenero
231:) is an
207:(verify)
106:ATC code
3543:lesions
3318:TGN1412
3203:PRO 140
2489:YouTube
2437:4594046
2222:4784892
2199:Bibcode
2163:3541671
2114:2990151
1998:7709430
1886:1702450
1877:1702450
1790:1420771
1453:1905242
1337:2195599
1288:1868523
1239:2193880
1032:Reuters
664:in vivo
573:placebo
550:Phase I
533:History
468:in vivo
325:Parexel
319:by the
306:T cells
294:agonist
252:Parexel
242:of the
221:TGN1412
18:TGN1412
3591:WHO-EM
3333:Other:
2444:
2434:
2363:Nature
2229:
2219:
2170:
2160:
2121:
2111:
2072:
2037:
1996:
1988:
1947:25 May
1920:
1884:
1874:
1797:
1787:
1721:4 June
1648:
1512:
1460:
1450:
1393:
1385:
1344:
1334:
1295:
1285:
1246:
1236:
1063:1 July
981:
973:
932:
669:T cell
585:
561:London
492:et al.
279:B cell
227:, and
75:Target
65:(from
58:Source
3551:Mouse
3384:Human
2882:Mouse
2848:Other
2611:Human
1994:S2CID
1968:Blood
1391:S2CID
1199:(PDF)
1188:(PDF)
1170:(PDF)
1163:(PDF)
1146:(PDF)
1139:(PDF)
258:), a
229:TAB08
67:mouse
2501:2020
2471:2019
2442:PMID
2393:170A
2370:2006
2344:2006
2314:2006
2288:2006
2257:2006
2227:PMID
2168:PMID
2119:PMID
2070:PMID
2035:PMID
1986:PMID
1949:2010
1918:PMID
1882:PMID
1795:PMID
1750:2017
1723:2010
1692:2022
1628:2006
1566:2006
1540:2006
1510:PMID
1458:PMID
1383:PMID
1342:PMID
1293:PMID
1244:PMID
1095:2006
1065:2021
1039:2020
1013:2024
979:PMID
971:ISSN
930:ISBN
798:IL-8
796:and
794:TNFα
640:and
612:and
610:skin
548:The
465:and
401:The
298:CD28
184:UNII
175:none
113:none
80:CD28
48:Type
2464:BBC
2432:PMC
2424:doi
2217:PMC
2207:doi
2158:PMC
2150:doi
2109:PMC
2101:doi
2097:161
2062:doi
2025:doi
2021:122
1976:doi
1972:109
1910:doi
1872:PMC
1864:doi
1785:PMC
1777:doi
1773:332
1769:BMJ
1500:doi
1496:355
1448:PMC
1440:doi
1436:115
1373:doi
1332:PMC
1324:doi
1320:190
1283:PMC
1275:doi
1271:123
1234:PMC
1226:doi
1222:197
1118:104
963:doi
959:283
779:of
620:in
527:HIV
409:sic
365:by
312:).
304:'s
250:by
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2418:.
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2274:.
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2193:.
2189:.
2166:.
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2144:.
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2117:.
2107:.
2095:.
2091:.
2068:.
2058:20
2056:.
2033:.
2019:.
2015:.
1992:.
1984:.
1970:.
1966:.
1939:.
1916:.
1906:45
1904:.
1880:.
1870:.
1858:.
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1793:.
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1771:.
1767:.
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1664:.
1619:.
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1470:^
1456:.
1446:.
1434:.
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1389:.
1381:.
1369:72
1367:.
1363:.
1340:.
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1073:^
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2233:.
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2174:.
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2125:.
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2076:.
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2041:.
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2000:.
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1801:.
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