663:, a molecule with ubiquitin ligase activity, was found to be induced by T cell receptor ligation (TCR) and suppressed by targeting the critical signaling intermediate PLC-gamma-1. The deletion of CISH in effector T cells dramatically augments TCR signaling and subsequent effector cytokine release, proliferation and survival. The adoptive transfer of tumor-specific effector T cells knocked out or knocked down CISH, resulting in a significant increase in functional avidity and sustained tumor immunity. Surprisingly no changes in activity of STAT5, CISH's purported target. Thus CISH represents a new class of T-cell intrinsic immunologic checkpoints with the potential to enhance adoptive immunotherapies.
639:, qualities otherwise thought to be important for antitumor efficacy. Differentiation state is inversely related to proliferation and persistence. Age is negatively correlated with clinical effectiveness. CD8 T cells can exist in a stem cell–like state, capable of clonal proliferation. Human T memory stem cells express a gene program that enables them to proliferate extensively and differentiate into other T cell populations.
1379:
expression. Approximately 10% of common cancers appear to express enough protein to be of interest for antitumor T cells. Low levels of some cancer-testes antigens are expressed in normal tissues, with associated toxicities. The NYESO-1 cancer-testes antigen has been targeted via a human TCR transduced into autologous cells. ORs were seen in 5 of 11 patients with metastatic melanoma and 4 of 6 patients with highly refractory
1375:
damage to gray matter in the brain, because this TCR also recognized a different but related epitope that is expressed at low levels in the brain. That CARs are potentially toxic to self-antigens was observed after infusion of CAR T cells specific for ERBB2. Two patients died when treated with an HLA-A1–restricted MAGE-A3–specific TCR whose affinity was enhanced by a site-specific mutagenesis.
131:
24:
116:
264:(TIL) and could stimulate regression of established lung and liver tumors. In 1986, human TILs from resected melanomas were found to contain cells that could recognize autologous tumors. In 1988 autologous TILs were shown to reduce metastatic melanoma tumors. Tumor-derived TILs are generally mixtures of
1352:
Several ongoing clinical trials of adoptive cell therapies are ongoing in solid tumors, but challenges in the development of such therapies for this type of malignancy include the lack of surface antigens that are not found on essential normal tissues, difficult-to-penetrate tumor stroma, and factors
530:
In melanoma, a resected melanoma specimen is digested into a single-cell suspension or divided into multiple tumor fragments. The result is individually grown in IL-2. Lymphocytes overgrow. They destroy the tumors in the sample within 2 to 3 weeks. They then produce pure cultures of lymphocytes that
1406:
Molecules shared among tumors and nonessential normal organs represent potential ACT targets, despite the related toxicity. For example, the CD19 molecule is expressed on more than 90% of B cell malignancies and on non-plasma B cells at all differentiation stages and has been successfully used to
1374:
Toxicities can also result when previously unknown cross-reactivities are seen that target normal self-proteins expressed in vital organs. Cancer-testes antigen MAGE-A3 is not known to be expressed in any normal tissues. However, targeting an HLA-A*0201–restricted peptide in MAGE-A3 caused severe
1378:
Cancer-testis antigens are a family of intracellular proteins that are expressed during fetal development, but with little expression in normal adult tissues. More than 100 such molecules are epigenetically up-regulated in from 10 to 80% of cancer types. However, they lack high levels of protein
631:
Improved antitumor responses have been seen in mouse and monkey models using T cells in early differentiation stages (such as naïve or central memory cells). CD8 T cells follow a progressive pathway of differentiation from naïve T cells into stem cell memory, central memory, effector memory, and
1366:
Targeting normal, nonmutated antigenic targets that are expressed on normal tissues, but overexpressed on tumors has led to severe on-target, off-tumor toxicity. Toxicity was encountered in patients who received high-avidity TCRs that recognized either the MART-1 or gp100 melanoma-melanocyte
291:
regimen administered immediately before TIL transfer increased cancer regression, as well as the persistent oligoclonal repopulation of the host with the transferred lymphocytes. In some patients, the administered antitumor cells represented up to 80% of the CD8 T cells months after the
249:, often without loss of effector functions. High doses of IL-2 could inhibit tumor growth in mice. 1982, studies demonstrated that intravenous immune lymphocytes could treat bulky subcutaneous FBL3 lymphomas. Administration of IL-2 after cell transfer enhanced therapeutic potential.
671:
Neither tumor bulk nor metastasis site affect the likelihood of achieving a complete cancer regression. Of 34 complete responders in two trials, one recurred. Only one patient with complete regression received more than one treatment. Prior treatment with targeted therapy using
586:
sequences were introduced into synthetic CAR or natural T-cell receptors to serve as a marker for identification, rapid purification, tailoring spacer length for optimal function and selective, antibody-coated, microbead-driven, large-scale expansion. This facilitates
322:
By 2010, doctors had begun experimental treatments for leukemia patients using CD19-targeted T cells with added DNA to stimulate cell division. As of 2015 trials had treated about 350 leukemia and lymphoma patients. Antigen CD19 appears only on
607:) were pioneered in the late 1980s and can be constructed by linking the variable regions of the antibody heavy and light chains to intracellular signaling chains such as CD3-zeta, potentially including costimulatory domains encoding
418:
In 2017, researchers announced the first use of donor cells (rather than the patients' own cells) to defeat leukemia in two infants for whom other treatments had failed. The cells had four genetic modifications. Two were made using
569:
is normally added to the extracted T cells to boost their effectiveness, but in high doses it can have a toxic effect. The reduced number of injected T cells is accompanied by reduced IL-2, thereby reducing side effects.
202:. The cells may have originated from the patient or from another individual. The cells are most commonly derived from the immune system with the goal of improving immune functionality and characteristics. In autologous
1397:
is another side effect and can be a function of therapeutic effectiveness. As the tumor is destroyed, it releases large quantities of cell signaling protein molecules. This effect killed at least seven patients.
642:
CD4 T cells can also promote tumor rejection. CD4 T cells enhance CD8 T cell function and can directly destroy tumor cells. Evidence suggests that T helper 17 cells can promote sustained antitumor immunity.
279:
published the first study in which a T cell's targeting receptor was replaced, and noted that this could be used to direct T cells to attack any kind of cell; this is the essential biotechnology underlying
1850:
603:
Antitumor receptors genetically engineered into normal T cells can be used for therapy. T cells can be redirected by the integration of genes encoding either conventional alpha-beta TCRs or CARs. CARs (
550:
administered for 5 days. This substantially increases infused cell persistence and the incidence and duration of clinical responses. Then cells and IL-2 at 720,000 IU/kg to tolerance are infused.
2500:
Palmer DC, Webber BR, Patel Y, Johnson MJ, Kariya CM, Lahr WS, et al. (2020-09-25). "Internal checkpoint regulates T cell neoantigen reactivity and susceptibility to PD1 blockade".
632:
ultimately terminally differentiated effector T cell populations. CD8 T cells paradoxically lose antitumor power as they acquire the ability to lyse target cells and to produce the
1793:
Kranz LM, Diken M, Haas H, Kreiter S, Loquai C, Reuter KC, et al. (June 2016). "Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy".
407:
In 2016, researchers developed a technique that used cancer cells' RNA to produce T cells and an immune response. They encased the RNA in a negatively charged fatty membrane.
34:
683:) did not affect the likelihood that melanoma patients would experience an objective response. Prior failed immunotherapies did not reduce the odds of objective response.
214:
and returned to the same patient. Comparatively, allogeneic therapies involve cells isolated and expanded from a donor separate from the patient receiving the cells.
651:
Other modes of enhancing immuno-therapy include targeting so-called intrinsic immune checkpoint blockades. Many of these intrinsic regulators include molecules with
1841:
420:
295:
Initially, melanoma was the only cancer that reproducibly yielded useful TIL cultures. In 2006 administration of normal circulating lymphocytes transduced with a
238:
lymphocytes were transferred from rodents heavily immunized against the tumor to inhibit growth of small established tumors, becoming the first example of ACT.
2869:"Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma"
1943:
731:
technology. One example of this in the case of T cell adoptive therapy is the addition of CARs to redirect the specificity of cytotoxic and helper T cells.
531:
can be tested for reactivity against other tumors, in coculture assays. Individual cultures are then expanded in the presence of IL-2 and excess irradiated
748:(TIL) or genetically re-directed peripheral blood mononuclear cells has been used experimentally to treat patients with advanced solid tumors, including
2771:"Clinical responses in a phase II study using adoptive transfer of short-term cultured tumor infiltration lymphocytes in metastatic melanoma patients"
1867:
3162:
1419:
and acute lymphoblastic leukemia. Toxicity against CD19 results in B cell loss in circulation and in bone marrow that can be overcome by periodic
2200:"Acquisition of full effector function in vitro paradoxically impairs the in vivo antitumor efficacy of adoptively transferred CD8+ T cells"
423:. One changed the cells so that they did not attack all the cells of another person. Another modification made tumor cells their target.
2918:"Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen"
95:
174:
3024:"T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia"
141:
67:
307:
melanoma-melanocyte antigen, mediated tumor regression. In 2010 administration of lymphocytes genetically engineered to express a
3157:
1716:
616:
1944:"Chitosan thermogels for local expansion and delivery of tumor-specific T lymphocytes towards enhanced cancer immunotherapies"
287:
Responses were often of short duration and faded days after administration. In 2002, lymphodepletion using a nonmyeloablative
74:
588:
261:
1746:"Acquisition of a CD19-negative myeloid phenotype allows immune escape of MLL-rearranged B-ALL from CD19 CAR-T-cell therapy"
745:
1416:
805:
532:
397:
81:
42:
156:
1688:
63:
152:
53:
38:
1455:
1394:
604:
389:
308:
281:
1979:
3136:
3126:
761:
2102:"Lineage relationship of CD8(+) T cell subsets is revealed by progressive changes in the epigenetic landscape"
1484:"Minimally cultured tumor-infiltrating lymphocytes display optimal characteristics for adoptive cell therapy"
431:
3167:
1447:
1367:
antigens, in mice when targeting melanocyte antigens, in patients with renal cancer using a CAR targeting
349:
regulation to remove inhibitory pathways that block T-cell responses, known as immune checkpoint therapy.
257:
3152:
1459:
1380:
342:
willingness to approve potential therapies for such ailments to accelerate approvals for new therapies.
2810:
Dudley ME, Wunderlich JR, Robbins PF, Yang JC, Hwu P, Schwartzentruber DJ, et al. (October 2002).
1386:"Suicide switches" let doctors kill engineered T cells in emergencies which threaten patient survival.
2978:
2823:
2812:"Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes"
2769:
Besser MJ, Shapira-Frommer R, Treves AJ, Zippel D, Itzhaki O, Hershkovitz L, et al. (May 2010).
2501:
2407:
1802:
1630:
1368:
753:
724:
203:
2247:
Muranski P, Borman ZA, Kerkar SP, Klebanoff CA, Ji Y, Sanchez-Perez L, et al. (December 2011).
88:
1482:
Tran KQ, Zhou J, Durflinger KH, Langhan MM, Shelton TE, Wunderlich JR, et al. (October 2008).
1412:
1408:
700:
563:
In early trials, preparing engineered T cells cost $ 75,000 to manufacture cells for each patient.
253:
3132:
1891:
Simon CG, Bozenhardt EH, Celluzzi CM, Dobnik D, Grant ML, Lakshmipathy U, et al. (May 2024).
2867:
Dudley ME, Wunderlich JR, Yang JC, Sherry RM, Topalian SL, Restifo NP, et al. (April 2005).
1826:
716:
692:
2965:
Morgan RA, Dudley ME, Wunderlich JR, Hughes MS, Yang JC, Sherry RM, et al. (October 2006).
627:
Correlations between T cell differentiation status, cellular persistence, and treatment outcomes
2198:
Gattinoni L, Klebanoff CA, Palmer DC, Wrzesinski C, Kerstann K, Yu Z, et al. (June 2005).
542:
Prior to infusion, a lymphodepleting preparative regimen is undergone, typically 60 mg/kg
539:
complex of the TCR. 5–6 weeks after resecting the tumor, up to 10 lymphocytes can be obtained.
3102:
3053:
3004:
2947:
2898:
2849:
2792:
2751:
2699:
2650:
2601:
2552:
2482:
2451:
Palmer DC, Guittard GC, Franco Z, Crompton JG, Eil RL, Patel SJ, et al. (November 2015).
2433:
2376:
2345:
Palmer DC, Guittard GC, Franco Z, Crompton JG, Eil RL, Patel SJ, et al. (November 2015).
2327:
2278:
2229:
2180:
2131:
2082:
2030:
1966:
1924:
1818:
1775:
1656:
1562:
1513:
821:
335:
3122:
2394:
Guittard G, Dios-Esponera A, Palmer DC, Akpan I, Barr VA, Manna A, et al. (March 2018).
2100:
Crompton JG, Narayanan M, Cuddapah S, Roychoudhuri R, Ji Y, Yang W, et al. (July 2016).
3092:
3084:
3043:
3035:
2994:
2986:
2937:
2929:
2888:
2880:
2839:
2831:
2782:
2741:
2733:
2689:
2681:
2640:
2632:
2591:
2583:
2542:
2534:
2472:
2464:
2423:
2415:
2366:
2358:
2317:
2309:
2268:
2260:
2219:
2211:
2170:
2162:
2121:
2113:
2072:
2064:
2020:
2012:
1958:
1914:
1904:
1810:
1765:
1757:
1646:
1638:
1552:
1544:
1503:
1495:
1463:
1462:
receptor family protein expressed on mature B cells and plasma cells and can be targeted on
777:
543:
536:
365:
2916:
Johnson LA, Morgan RA, Dudley ME, Cassard L, Yang JC, Hughes MS, et al. (July 2009).
765:
728:
720:
708:
353:
316:
300:
636:
2982:
2827:
2411:
2296:
Muranski P, Boni A, Antony PA, Cassard L, Irvine KR, Kaiser A, et al. (July 2008).
2149:
Gattinoni L, Lugli E, Ji Y, Pos Z, Paulos CM, Quigley MF, et al. (September 2011).
1919:
1892:
1806:
1634:
3097:
3072:
3048:
3023:
2999:
2966:
2942:
2917:
2893:
2868:
2844:
2811:
2746:
2721:
2694:
2669:
2645:
2620:
2596:
2571:
2547:
2522:
2477:
2452:
2428:
2395:
2371:
2346:
2322:
2297:
2273:
2248:
2224:
2199:
2175:
2150:
2126:
2101:
2077:
2052:
2025:
2000:
1962:
1770:
1745:
1651:
1618:
1557:
1532:
1508:
1483:
1420:
673:
553:
412:
328:
195:
2396:"The Cish SH2 domain is essential for PLC-γ1 regulation in TCR stimulated CD8 T cells"
1533:"Allogeneic adoptive cell transfer therapy as a potent universal treatment for cancer"
1450:, though the expression of these molecules on normal precursors can lead to prolonged
699:. Clinically, this approach has been exploited to transfer either immune-promoting or
392:(CAR)-modified T cells were used to treat patients with relapsed and refractory CD19+
3146:
1451:
789:
781:
620:
566:
377:
369:
252:
In 1985 IL-2 administration produced durable tumor regressions in some patients with
242:
3022:
Kalos M, Levine BL, Porter DL, Katz S, Grupp SA, Bagg A, et al. (August 2011).
2967:"Cancer regression in patients after transfer of genetically engineered lymphocytes"
1830:
2001:"Inclusion of Strep-tag II in design of antigen receptors for T-cell immunotherapy"
288:
276:
2787:
2770:
2722:"Human T regulatory cell therapy: take a billion or so and call me in the morning"
2453:"Cish actively silences TCR signaling in CD8+ T cells to maintain tumor tolerance"
2347:"Cish actively silences TCR signaling in CD8+ T cells to maintain tumor tolerance"
595:
tracking and retrieval of transferred cells for downstream research applications.
3088:
3039:
2933:
2737:
2313:
2264:
1761:
1744:
Gardner R, Wu D, Cherian S, Fang M, Hanafi LA, Finney O, et al. (May 2016).
1499:
785:
704:
676:
660:
656:
547:
507:
373:
327:, which go awry in lymphoma and leukemia. Loss of B cells can be countered with
223:
2419:
1909:
426:
As of
February 2024, 27 advanced cell therapy products (CTPs) were approved by
2506:
1893:"Mechanism of action, potency and efficacy: considerations for cell therapies"
696:
455:
296:
1999:
Liu L, Sommermeyer D, Cabanov A, Kosasih P, Hill T, Riddell SR (April 2016).
1353:
in the tumor microenvironment that impede the activity of the immune system.
2990:
2884:
2835:
1642:
1548:
652:
615:. CARs can provide recognition of cell surface components not restricted to
583:
579:
447:
235:
227:
3106:
3057:
3008:
2951:
2902:
2853:
2796:
2755:
2703:
2654:
2605:
2556:
2486:
2437:
2380:
2331:
2282:
2249:"Th17 cells are long lived and retain a stem cell-like molecular signature"
2233:
2184:
2135:
2086:
2034:
1970:
1928:
1822:
1779:
1660:
1566:
1517:
2298:"Tumor-specific Th17-polarized cells eradicate large established melanoma"
1868:"Two infants treated with universal immune cells have their cancer vanish"
2685:
2468:
2362:
1435:
1059:
797:
773:
769:
749:
680:
633:
515:
511:
499:
495:
483:
479:
471:
467:
463:
451:
443:
435:
385:
361:
357:
2117:
1814:
1942:
Monette A, Ceccaldi C, Assaad E, Lerouge S, Lapointe R (January 2016).
1619:"Adoptive cell transfer as personalized immunotherapy for human cancer"
1426:
Multiple other B cell antigens are being studied as targets, including
793:
519:
503:
491:
487:
459:
381:
324:
199:
52:
if you can. Unsourced or poorly sourced material may be challenged and
2053:"Prospects for gene-engineered T cell immunotherapy for solid cancers"
1717:"Dramatic remissions in blood cancer in immunotherapy treatment trial"
619:(MHC). They can be introduced into T cells with high efficiency using
2636:
2215:
2016:
1331:
801:
712:
556:
may play an important role in enhancing the efficacy of T cell based
475:
439:
393:
346:
304:
231:
207:
2587:
2538:
2166:
2068:
591:
manufacturing of pure populations of engineered T cells and enables
411:, this electrical charge guided the particles towards the patient's
260:
of growing, transplantable tumors provided a concentrated source of
230:
rejection in animals. Attempts to use T cells to treat transplanted
159:. Statements consisting only of original research should be removed.
727:. Cells used in adoptive therapy may be genetically modified using
1443:
809:
612:
401:
210:
are extracted from the patient, genetically modified and cultured
234:
tumors required cultivating and manipulating T cells in culture.
1439:
1431:
1427:
1106:
757:
608:
345:
In checkpoint therapy, antibodies bind to molecules involved in
312:
427:
339:
269:
265:
124:
17:
2570:
Gattinoni L, Powell DJ, Rosenberg SA, Restifo NP (May 2006).
2151:"A human memory T cell subset with stem cell-like properties"
832:
Trials began in the 1990s and accelerated beginning in 2010.
574:
tests on melanoma and kidney cancer models met expectations.
2523:"Paths to stemness: building the ultimate antitumour T cell"
1842:"'Universal cancer vaccine' breakthrough claimed by experts"
1438:
expressed by the individual cancer. CARs targeting either
535:. The latter targets the epsilon subunit within the human
2668:
Schmitt TM, Ragnarsson GB, Greenberg PD (November 2009).
2572:"Adoptive immunotherapy for cancer: building on success"
2051:
Klebanoff CA, Rosenberg SA, Restifo NP (January 2016).
148:
49:
3073:"CAR T cells for solid tumors: armed and ready to go?"
2521:
Gattinoni L, Klebanoff CA, Restifo NP (October 2012).
1371:and in patients with metastatic colorectal cancer.
824:has been used to treat Type 1 diabetes and others.
2621:"Adoptive T cell therapy for cancer in the clinic"
1840:
272: T cells with few major contaminating cells.
1446:have been studied as a therapy for patients with
338:exploit the combination of aggressive tumors and
245:(IL-2) in 1976 allowed T lymphocytes to be grown
2046:
2044:
1984:University of Montreal Hospital Research Centre
1318:First report targeting nonmelanoma solid tumor
1070:Clones reactive against cancer-testes antigens
352:As of 2015 the technique had expanded to treat
315:was shown to mediate regression of an advanced
48:Please review the contents of the article and
647:Intrinsic (Intracellular) checkpoint blockade
8:
2715:
2713:
1434:, ROR-1 and the immunoglobulin light-chain
498:; and various other cell therapy products (
715:or to promote tolerance in the setting of
3135:at the U.S. National Library of Medicine
3125:at the U.S. National Library of Medicine
3096:
3047:
2998:
2941:
2892:
2843:
2786:
2745:
2720:Riley JL, June CH, Blazar BR (May 2009).
2693:
2670:"T cell receptor gene therapy for cancer"
2644:
2595:
2546:
2505:
2476:
2427:
2370:
2321:
2272:
2223:
2174:
2125:
2076:
2024:
1918:
1908:
1769:
1650:
1556:
1507:
175:Learn how and when to remove this message
834:
695:for various diseases is the transfer of
1617:Rosenberg SA, Restifo NP (April 2015).
1612:
1610:
1608:
1606:
1604:
1602:
1600:
1598:
1596:
1474:
808:(B-ALL) harboring rearrangement of the
400:(B-ALL) harboring rearrangement of the
226:were discovered to be the mediators of
3071:Kakarla S, Gottschalk S (2014-01-01).
1682:
1680:
1678:
1676:
1674:
1672:
1670:
1594:
1592:
1590:
1588:
1586:
1584:
1582:
1580:
1578:
1576:
1161:Four of five then underwent allo-HSCT
1092:Many treated at high risk for relapse
1045:Selected to target a somatic mutation
2625:The Journal of Clinical Investigation
2204:The Journal of Clinical Investigation
919:Lymphodepletion before cell transfer
707:) to either enhance immunity against
7:
2457:The Journal of Experimental Medicine
2351:The Journal of Experimental Medicine
1739:
1737:
1711:
1709:
744:The adoptive transfer of autologous
415:that specify immune system targets.
241:Description of T cell growth factor
2106:Cellular & Molecular Immunology
1963:10.1016/j.biomaterials.2015.10.021
617:major histocompatibility complexes
404:(MLL) gene with CD19 CAR-T cells.
14:
1897:Journal of Translational Medicine
1270:CR2 CARs into EBV-reactive cells
1139:Lentivirus used for transduction
1980:"Intelligent gel attacks cancer"
1853:from the original on 2016-06-01.
1531:Marcus A, Eshhar Z (July 2011).
1300:Genetically engineered with TCRs
1097:Genetically engineered with CARs
1023:Probably targeting HPV antigens
1002:Intention to treat: 29% OR rate
981:Intention to treat: 26% OR rate
800:, relapsed and refractory CD19+
129:
114:
22:
861:Tumor-infiltrating lymphocytes*
804:malignancies, including B cell
396:malignancies, including B cell
256:. Lymphocytes infiltrating the
3163:Experimental cancer treatments
3028:Science Translational Medicine
1689:"Biotech's Coming Cancer Cure"
746:tumor infiltrating lymphocytes
262:tumor-infiltrating lymphocytes
50:add the appropriate references
1:
2788:10.1158/1078-0432.CCR-10-0041
1839:Ian Johnston (June 1, 2016).
311:(CAR) against B cell antigen
3089:10.1097/PPO.0000000000000032
3040:10.1126/scitranslmed.3002842
2934:10.1182/blood-2009-03-211714
2873:Journal of Clinical Oncology
2738:10.1016/j.immuni.2009.04.006
2314:10.1182/blood-2007-11-120998
2265:10.1016/j.immuni.2011.09.019
1762:10.1182/blood-2015-08-665547
1687:Regalado A (June 18, 2015).
1500:10.1097/CJI.0b013e31818403d5
1417:chronic lymphocytic leukemia
806:acute lymphoblastic leukemia
546:for 2 days and 25 mg/m
398:acute lymphoblastic leukemia
1117:First use of anti-CD19 CAR
756:, as well as patients with
655:ligase activity, including
605:Chimeric Antibody Receptors
155:the claims made and adding
35:reliable medical references
3184:
2576:Nature Reviews. Immunology
2420:10.1038/s41598-018-23549-2
1910:10.1186/s12967-024-05179-7
1204:Four of seven CR in DLBCL
309:chimeric antibody receptor
303:(TCR) that recognized the
2507:10.1101/2020.09.24.306571
1395:Cytokine release syndrome
1390:Cytokine release syndrome
442:, Lifesouth, Bloodworks,
390:chimeric antigen receptor
388:. In 2016, CD19-specific
41:or relies too heavily on
3137:Medical Subject Headings
3127:Medical Subject Headings
2775:Clinical Cancer Research
1488:Journal of Immunotherapy
1226:Many moved to allo-HSCT
762:hematologic malignancies
64:"Adoptive cell transfer"
3158:Cell culture techniques
2991:10.1126/science.1129003
2885:10.1200/JCO.2005.00.240
2836:10.1126/science.1076514
1643:10.1126/science.aaa4967
1549:10.18632/oncotarget.300
1295:2016;126(6):2123–2138.
432:hematopoietic stem cell
3133:Adoptive Immunotherapy
2527:Nature Reviews. Cancer
1448:acute myeloid leukemia
1248:Dose-escalation study
1050:In vitro sensitization
940:20% CR beyond 5 years
810:mixed lineage leukemia
413:dendritic immune cells
402:mixed lineage leukemia
188:Adoptive cell transfer
2619:June CH (June 2007).
1872:MIT Technology Review
1460:tumor necrosis factor
1381:synovial cell sarcoma
878:Original use TIL ACT
194:) is the transfer of
2686:10.1089/hum.2009.146
2469:10.1084/jem.20150304
2363:10.1084/jem.20150304
2005:Nature Biotechnology
1986:. November 19, 2015.
1413:large-cell lymphomas
1407:treat patients with
1369:carbonic anhydrase 9
754:colorectal carcinoma
725:rheumatoid arthritis
204:cancer immunotherapy
2983:2006Sci...314..126M
2828:2002Sci...298..850D
2412:2018NatSR...8.5336G
2118:10.1038/cmi.2015.32
1815:10.1038/nature18300
1807:2016Natur.534..396K
1635:2015Sci...348...62R
1409:follicular lymphoma
599:Genetic engineering
533:anti-CD3 antibodies
334:Startups including
254:metastatic melanoma
2674:Human Gene Therapy
2400:Scientific Reports
1721:www.kurzweilai.net
822:regulatory T cells
816:Autoimmune disease
717:autoimmune disease
693:treatment modality
482:); gene therapies
140:possibly contains
3123:Adoptive Transfer
2977:(5796): 126–129.
2879:(10): 2346–2357.
2822:(5594): 850–854.
2680:(11): 1240–1248.
2463:(12): 2095–2113.
2357:(12): 2095–2113.
2161:(10): 1290–1297.
1801:(7607): 396–401.
1756:(20): 2406–2410.
1693:Technology Review
1345:
1344:
659:. More recently,
430:. These included
336:Juno Therapeutics
185:
184:
177:
142:original research
123:
122:
99:
3175:
3111:
3110:
3100:
3068:
3062:
3061:
3051:
3019:
3013:
3012:
3002:
2962:
2956:
2955:
2945:
2913:
2907:
2906:
2896:
2864:
2858:
2857:
2847:
2807:
2801:
2800:
2790:
2781:(9): 2646–2655.
2766:
2760:
2759:
2749:
2717:
2708:
2707:
2697:
2665:
2659:
2658:
2648:
2637:10.1172/JCI32446
2631:(6): 1466–1476.
2616:
2610:
2609:
2599:
2567:
2561:
2560:
2550:
2518:
2512:
2511:
2509:
2497:
2491:
2490:
2480:
2448:
2442:
2441:
2431:
2391:
2385:
2384:
2374:
2342:
2336:
2335:
2325:
2293:
2287:
2286:
2276:
2244:
2238:
2237:
2227:
2216:10.1172/JCI24480
2210:(6): 1616–1626.
2195:
2189:
2188:
2178:
2146:
2140:
2139:
2129:
2097:
2091:
2090:
2080:
2048:
2039:
2038:
2028:
2017:10.1038/nbt.3461
1996:
1990:
1987:
1977:Lay summary in:
1974:
1948:
1939:
1933:
1932:
1922:
1912:
1888:
1882:
1881:
1879:
1878:
1863:
1857:
1854:
1844:
1837:Lay summary in:
1834:
1790:
1784:
1783:
1773:
1741:
1732:
1731:
1729:
1728:
1723:. March 10, 2016
1713:
1704:
1703:
1701:
1699:
1684:
1665:
1664:
1654:
1614:
1571:
1570:
1560:
1528:
1522:
1521:
1511:
1479:
1464:multiple myeloma
1306:Synovial sarcoma
847:Molecular target
844:Cancer histology
835:
820:The transfer of
778:bile duct cancer
544:cyclophosphamide
366:bile duct cancer
180:
173:
169:
166:
160:
157:inline citations
133:
132:
125:
118:
117:
109:
106:
100:
98:
57:
26:
25:
18:
3183:
3182:
3178:
3177:
3176:
3174:
3173:
3172:
3143:
3142:
3119:
3114:
3070:
3069:
3065:
3021:
3020:
3016:
2964:
2963:
2959:
2915:
2914:
2910:
2866:
2865:
2861:
2809:
2808:
2804:
2768:
2767:
2763:
2719:
2718:
2711:
2667:
2666:
2662:
2618:
2617:
2613:
2588:10.1038/nri1842
2569:
2568:
2564:
2539:10.1038/nrc3322
2533:(10): 671–684.
2520:
2519:
2515:
2499:
2498:
2494:
2450:
2449:
2445:
2393:
2392:
2388:
2344:
2343:
2339:
2295:
2294:
2290:
2246:
2245:
2241:
2197:
2196:
2192:
2167:10.1038/nm.2446
2155:Nature Medicine
2148:
2147:
2143:
2099:
2098:
2094:
2069:10.1038/nm.4015
2057:Nature Medicine
2050:
2049:
2042:
1998:
1997:
1993:
1978:
1946:
1941:
1940:
1936:
1890:
1889:
1885:
1876:
1874:
1865:
1864:
1860:
1847:The Independent
1838:
1792:
1791:
1787:
1743:
1742:
1735:
1726:
1724:
1715:
1714:
1707:
1697:
1695:
1686:
1685:
1668:
1629:(6230): 62–68.
1616:
1615:
1574:
1530:
1529:
1525:
1481:
1480:
1476:
1472:
1404:
1392:
1364:
1359:
1350:
1012:Cervical cancer
830:
818:
766:cervical cancer
742:
737:
729:recombinant DNA
721:Type I diabetes
689:
669:
649:
629:
601:
528:
354:cervical cancer
317:B cell lymphoma
301:T-cell receptor
220:
181:
170:
164:
161:
146:
134:
130:
119:
115:
110:
104:
101:
58:
47:
43:primary sources
27:
23:
12:
11:
5:
3181:
3179:
3171:
3170:
3165:
3160:
3155:
3145:
3144:
3141:
3140:
3130:
3118:
3117:External links
3115:
3113:
3112:
3083:(2): 151–155.
3077:Cancer Journal
3063:
3034:(95): 95ra73.
3014:
2957:
2928:(3): 535–546.
2908:
2859:
2802:
2761:
2732:(5): 656–665.
2709:
2660:
2611:
2582:(5): 383–393.
2562:
2513:
2492:
2443:
2386:
2337:
2308:(2): 362–373.
2288:
2259:(6): 972–985.
2239:
2190:
2141:
2112:(4): 502–513.
2092:
2040:
2011:(4): 430–434.
1991:
1989:
1988:
1934:
1883:
1858:
1856:
1855:
1785:
1733:
1705:
1666:
1572:
1543:(7): 525–526.
1523:
1494:(8): 742–751.
1473:
1471:
1468:
1421:immunoglobulin
1403:
1400:
1391:
1388:
1363:
1360:
1358:
1355:
1349:
1346:
1343:
1342:
1340:
1337:
1334:
1329:
1326:
1323:
1320:
1319:
1316:
1313:
1310:
1307:
1304:
1301:
1297:
1296:
1293:J Clin Invest.
1290:
1287:
1284:
1281:
1278:
1275:
1272:
1271:
1268:
1265:
1262:
1259:
1256:
1253:
1250:
1249:
1246:
1243:
1240:
1237:
1234:
1231:
1228:
1227:
1224:
1221:
1218:
1215:
1212:
1209:
1206:
1205:
1202:
1199:
1196:
1194:
1191:
1188:
1185:
1184:
1181:
1178:
1175:
1172:
1169:
1166:
1163:
1162:
1159:
1156:
1153:
1150:
1147:
1144:
1141:
1140:
1137:
1134:
1131:
1128:
1125:
1122:
1119:
1118:
1115:
1112:
1109:
1104:
1101:
1098:
1094:
1093:
1090:
1087:
1084:
1081:
1078:
1075:
1072:
1071:
1068:
1065:
1062:
1057:
1054:
1051:
1047:
1046:
1043:
1040:
1037:
1034:
1031:
1028:
1025:
1024:
1021:
1018:
1015:
1013:
1010:
1007:
1004:
1003:
1000:
997:
994:
992:
989:
986:
983:
982:
979:
976:
973:
971:
968:
965:
962:
961:
959:
956:
953:
951:
948:
945:
942:
941:
938:
935:
932:
930:
927:
924:
921:
920:
917:
914:
911:
909:
906:
903:
900:
899:
897:
894:
891:
889:
886:
883:
880:
879:
876:
873:
870:
868:
865:
862:
858:
857:
854:
851:
848:
845:
842:
839:
829:
826:
817:
814:
741:
738:
736:
733:
688:
685:
674:Braf inhibitor
668:
665:
648:
645:
628:
625:
600:
597:
554:Interleukin-21
527:
524:
438:, Clinimmune,
329:immunoglobulin
222:In the 1960s,
219:
216:
183:
182:
137:
135:
128:
121:
120:
113:
111:
30:
28:
21:
13:
10:
9:
6:
4:
3:
2:
3180:
3169:
3168:Immunotherapy
3166:
3164:
3161:
3159:
3156:
3154:
3151:
3150:
3148:
3138:
3134:
3131:
3128:
3124:
3121:
3120:
3116:
3108:
3104:
3099:
3094:
3090:
3086:
3082:
3078:
3074:
3067:
3064:
3059:
3055:
3050:
3045:
3041:
3037:
3033:
3029:
3025:
3018:
3015:
3010:
3006:
3001:
2996:
2992:
2988:
2984:
2980:
2976:
2972:
2968:
2961:
2958:
2953:
2949:
2944:
2939:
2935:
2931:
2927:
2923:
2919:
2912:
2909:
2904:
2900:
2895:
2890:
2886:
2882:
2878:
2874:
2870:
2863:
2860:
2855:
2851:
2846:
2841:
2837:
2833:
2829:
2825:
2821:
2817:
2813:
2806:
2803:
2798:
2794:
2789:
2784:
2780:
2776:
2772:
2765:
2762:
2757:
2753:
2748:
2743:
2739:
2735:
2731:
2727:
2723:
2716:
2714:
2710:
2705:
2701:
2696:
2691:
2687:
2683:
2679:
2675:
2671:
2664:
2661:
2656:
2652:
2647:
2642:
2638:
2634:
2630:
2626:
2622:
2615:
2612:
2607:
2603:
2598:
2593:
2589:
2585:
2581:
2577:
2573:
2566:
2563:
2558:
2554:
2549:
2544:
2540:
2536:
2532:
2528:
2524:
2517:
2514:
2508:
2503:
2496:
2493:
2488:
2484:
2479:
2474:
2470:
2466:
2462:
2458:
2454:
2447:
2444:
2439:
2435:
2430:
2425:
2421:
2417:
2413:
2409:
2405:
2401:
2397:
2390:
2387:
2382:
2378:
2373:
2368:
2364:
2360:
2356:
2352:
2348:
2341:
2338:
2333:
2329:
2324:
2319:
2315:
2311:
2307:
2303:
2299:
2292:
2289:
2284:
2280:
2275:
2270:
2266:
2262:
2258:
2254:
2250:
2243:
2240:
2235:
2231:
2226:
2221:
2217:
2213:
2209:
2205:
2201:
2194:
2191:
2186:
2182:
2177:
2172:
2168:
2164:
2160:
2156:
2152:
2145:
2142:
2137:
2133:
2128:
2123:
2119:
2115:
2111:
2107:
2103:
2096:
2093:
2088:
2084:
2079:
2074:
2070:
2066:
2062:
2058:
2054:
2047:
2045:
2041:
2036:
2032:
2027:
2022:
2018:
2014:
2010:
2006:
2002:
1995:
1992:
1985:
1981:
1976:
1975:
1972:
1968:
1964:
1960:
1956:
1952:
1945:
1938:
1935:
1930:
1926:
1921:
1916:
1911:
1906:
1902:
1898:
1894:
1887:
1884:
1873:
1869:
1862:
1859:
1852:
1848:
1843:
1836:
1835:
1832:
1828:
1824:
1820:
1816:
1812:
1808:
1804:
1800:
1796:
1789:
1786:
1781:
1777:
1772:
1767:
1763:
1759:
1755:
1751:
1747:
1740:
1738:
1734:
1722:
1718:
1712:
1710:
1706:
1694:
1690:
1683:
1681:
1679:
1677:
1675:
1673:
1671:
1667:
1662:
1658:
1653:
1648:
1644:
1640:
1636:
1632:
1628:
1624:
1620:
1613:
1611:
1609:
1607:
1605:
1603:
1601:
1599:
1597:
1595:
1593:
1591:
1589:
1587:
1585:
1583:
1581:
1579:
1577:
1573:
1568:
1564:
1559:
1554:
1550:
1546:
1542:
1538:
1534:
1527:
1524:
1519:
1515:
1510:
1505:
1501:
1497:
1493:
1489:
1485:
1478:
1475:
1469:
1467:
1465:
1461:
1457:
1453:
1452:myeloablation
1449:
1445:
1441:
1437:
1433:
1429:
1424:
1422:
1418:
1414:
1410:
1401:
1399:
1396:
1389:
1387:
1384:
1382:
1376:
1372:
1370:
1361:
1356:
1354:
1347:
1341:
1338:
1335:
1333:
1330:
1327:
1324:
1322:
1321:
1317:
1314:
1311:
1308:
1305:
1302:
1299:
1298:
1294:
1291:
1288:
1285:
1282:
1279:
1276:
1274:
1273:
1269:
1266:
1263:
1260:
1258:Neuroblastoma
1257:
1254:
1252:
1251:
1247:
1244:
1241:
1238:
1235:
1232:
1230:
1229:
1225:
1222:
1219:
1216:
1213:
1210:
1208:
1207:
1203:
1200:
1197:
1195:
1192:
1189:
1187:
1186:
1182:
1179:
1176:
1173:
1170:
1167:
1165:
1164:
1160:
1157:
1154:
1151:
1148:
1145:
1143:
1142:
1138:
1135:
1132:
1129:
1126:
1123:
1121:
1120:
1116:
1113:
1110:
1108:
1105:
1102:
1099:
1096:
1095:
1091:
1088:
1085:
1082:
1079:
1076:
1074:
1073:
1069:
1066:
1063:
1061:
1058:
1055:
1052:
1049:
1048:
1044:
1041:
1038:
1035:
1032:
1029:
1027:
1026:
1022:
1019:
1016:
1014:
1011:
1008:
1006:
1005:
1001:
998:
995:
993:
990:
987:
985:
984:
980:
977:
974:
972:
969:
966:
964:
963:
960:
957:
954:
952:
949:
946:
944:
943:
939:
936:
933:
931:
928:
925:
923:
922:
918:
915:
912:
910:
907:
904:
902:
901:
898:
895:
892:
890:
887:
884:
882:
881:
877:
874:
871:
869:
866:
863:
860:
859:
855:
853:Number of ORs
852:
849:
846:
843:
840:
837:
836:
833:
828:Trial results
827:
825:
823:
815:
813:
811:
807:
803:
799:
795:
791:
790:breast cancer
787:
783:
782:neuroblastoma
779:
775:
771:
767:
763:
759:
755:
751:
747:
739:
734:
732:
730:
726:
722:
718:
714:
710:
706:
703:cells (often
702:
698:
694:
686:
684:
682:
678:
675:
666:
664:
662:
658:
654:
646:
644:
640:
638:
635:
626:
624:
622:
621:viral vectors
618:
614:
610:
606:
598:
596:
594:
590:
585:
582:
581:
575:
573:
568:
567:Interleukin-2
564:
561:
559:
555:
551:
549:
545:
540:
538:
534:
525:
523:
521:
517:
513:
509:
505:
501:
497:
493:
489:
485:
481:
477:
473:
469:
465:
461:
457:
453:
449:
445:
441:
437:
433:
429:
424:
422:
416:
414:
410:
405:
403:
399:
395:
391:
387:
383:
379:
378:breast cancer
375:
372:and in 2016,
371:
370:neuroblastoma
367:
363:
359:
355:
350:
348:
343:
341:
337:
332:
330:
326:
320:
318:
314:
310:
306:
302:
298:
293:
290:
285:
283:
278:
273:
271:
267:
263:
259:
255:
250:
248:
244:
243:interleukin-2
239:
237:
233:
229:
225:
217:
215:
213:
209:
205:
201:
197:
193:
189:
179:
176:
168:
158:
154:
150:
144:
143:
138:This article
136:
127:
126:
112:
108:
97:
94:
90:
87:
83:
80:
76:
73:
69:
66: –
65:
61:
60:Find sources:
55:
51:
45:
44:
40:
36:
31:This article
29:
20:
19:
16:
3153:Cell biology
3080:
3076:
3066:
3031:
3027:
3017:
2974:
2970:
2960:
2925:
2921:
2911:
2876:
2872:
2862:
2819:
2815:
2805:
2778:
2774:
2764:
2729:
2725:
2677:
2673:
2663:
2628:
2624:
2614:
2579:
2575:
2565:
2530:
2526:
2516:
2495:
2460:
2456:
2446:
2403:
2399:
2389:
2354:
2350:
2340:
2305:
2301:
2291:
2256:
2252:
2242:
2207:
2203:
2193:
2158:
2154:
2144:
2109:
2105:
2095:
2063:(1): 26–36.
2060:
2056:
2008:
2004:
1994:
1983:
1954:
1951:Biomaterials
1950:
1937:
1900:
1896:
1886:
1875:. Retrieved
1871:
1866:Regalado A.
1861:
1846:
1798:
1794:
1788:
1753:
1749:
1725:. Retrieved
1720:
1696:. Retrieved
1692:
1626:
1622:
1540:
1536:
1526:
1491:
1487:
1477:
1425:
1405:
1393:
1385:
1377:
1373:
1365:
1351:
1348:Solid tumors
1292:
1036:Mutated ERB2
831:
819:
760:-expressing
743:
735:Applications
691:An emerging
690:
670:
650:
641:
637:interferon-γ
630:
602:
592:
578:
576:
571:
565:
562:
557:
552:
541:
529:
425:
417:
408:
406:
351:
344:
333:
321:
294:
289:chemotherapy
286:
277:Zelig Eshhar
274:
251:
246:
240:
221:
211:
191:
187:
186:
171:
162:
139:
102:
92:
85:
78:
71:
59:
39:verification
32:
15:
2406:(1): 5336.
1957:: 237–249.
1423:infusions.
786:lung cancer
705:lymphocytes
701:tolerogenic
677:vemurafenib
560:therapies.
548:fludarabine
508:Stratagraft
374:lung cancer
299:encoding a
224:lymphocytes
33:needs more
3147:Categories
1903:(1): 416.
1877:2017-01-27
1727:2016-03-13
1698:16 October
1537:Oncotarget
1470:References
1183:CR in 90%
719:, such as
697:stem cells
687:Stem cells
458:products (
434:products (
297:retrovirus
292:infusion.
268: and
149:improve it
75:newspapers
1033:Bile duct
856:Comments
653:ubiquitin
502:, Laviv,
448:Clevecord
284:therapy.
236:Syngeneic
228:allograft
165:June 2018
153:verifying
105:June 2018
3107:24667962
3058:21832238
3009:16946036
2952:19451549
2903:15800326
2854:12242449
2797:20406835
2756:19464988
2726:Immunity
2704:19702439
2655:17549249
2606:16622476
2557:22996603
2487:26527801
2438:29593227
2381:26527801
2332:18354038
2283:22177921
2253:Immunity
2234:15931392
2185:21926977
2136:25914936
2087:26735408
2035:26900664
1971:26513416
1929:38698408
1920:11067168
1851:Archived
1831:38112227
1823:27281205
1780:26907630
1661:25838374
1567:21719916
1518:18779745
1436:idiotype
1362:Toxicity
1328:Melanoma
1309:NY-ESO-1
1193:Lymphoma
1103:Lymphoma
1080:Leukemia
1060:NY-ESO-1
1056:Melanoma
991:Melanoma
970:Melanoma
950:Melanoma
929:Melanoma
908:Melanoma
888:Melanoma
867:Melanoma
850:Patients
798:melanoma
774:leukemia
770:lymphoma
750:melanoma
681:Zelboraf
634:cytokine
577:In 2016
572:In vitro
558:in vitro
516:Lantidra
512:Rethymic
506:, Maci,
500:Provenge
496:Lyfgenia
484:Zynteglo
480:Carvykti
472:Breyanzi
468:Tecartus
464:Yescarta
452:Omisirge
444:Allocord
436:Hemacord
386:melanoma
362:leukemia
358:lymphoma
275:In 1989
247:in vitro
212:in vitro
3098:4050065
3049:3393096
3000:2267026
2979:Bibcode
2971:Science
2943:2929689
2894:1475951
2845:1764179
2824:Bibcode
2816:Science
2747:2742482
2695:2829456
2646:1878537
2597:1473162
2548:6352980
2502:bioRxiv
2478:4647263
2429:5871872
2408:Bibcode
2372:4647263
2323:2442746
2274:3246082
2225:1137001
2176:3192229
2127:4947817
2078:6295670
2026:4940167
1803:Bibcode
1771:4874221
1652:6295668
1631:Bibcode
1623:Science
1558:3248176
1509:2614999
1402:B cells
812:(MLL).
794:sarcoma
709:viruses
667:Context
593:in vivo
584:-tag II
526:Process
520:Amtagvi
504:Gintuit
492:Skysona
488:Casgevy
460:Kymriah
409:In vivo
382:sarcoma
325:B cells
218:History
208:T cells
200:patient
198:into a
147:Please
89:scholar
54:removed
3139:(MeSH)
3129:(MeSH)
3105:
3095:
3056:
3046:
3007:
2997:
2950:
2940:
2901:
2891:
2852:
2842:
2795:
2754:
2744:
2702:
2692:
2653:
2643:
2604:
2594:
2555:
2545:
2504:
2485:
2475:
2436:
2426:
2379:
2369:
2330:
2320:
2281:
2271:
2232:
2222:
2183:
2173:
2134:
2124:
2085:
2075:
2033:
2023:
1969:
1927:
1917:
1829:
1821:
1795:Nature
1778:
1768:
1659:
1649:
1565:
1555:
1516:
1506:
1357:Safety
1332:MART-1
802:B cell
740:Cancer
713:cancer
518:, and
494:, and
478:, and
476:Abecma
450:, and
440:Ducord
421:TALENs
394:B cell
347:T-cell
305:MART-1
258:stroma
232:murine
91:
84:
77:
70:
62:
2922:Blood
2302:Blood
1947:(PDF)
1827:S2CID
1750:Blood
1458:is a
1444:CD123
1283:CD19
1277:2016
838:Cells
613:CD137
580:Strep
282:CAR-T
196:cells
96:JSTOR
82:books
3103:PMID
3054:PMID
3005:PMID
2948:PMID
2899:PMID
2850:PMID
2793:PMID
2752:PMID
2700:PMID
2651:PMID
2602:PMID
2553:PMID
2483:PMID
2434:PMID
2377:PMID
2328:PMID
2279:PMID
2230:PMID
2181:PMID
2132:PMID
2083:PMID
2031:PMID
1967:PMID
1925:PMID
1819:PMID
1776:PMID
1700:2016
1657:PMID
1563:PMID
1514:PMID
1456:BCMA
1440:CD33
1432:CD23
1428:CD22
1325:2006
1303:2011
1289:93%
1280:ALL
1255:2011
1239:CD19
1233:2014
1217:CD19
1211:2014
1190:2014
1174:CD19
1168:2014
1158:100%
1152:CD19
1146:2013
1136:100%
1130:CD19
1124:2011
1114:100%
1107:CD19
1100:2010
1083:WT-1
1077:2014
1053:2008
1030:2014
1009:2014
988:2013
967:2012
947:2012
926:2011
905:2002
885:1994
864:1998
841:Year
780:and
758:CD19
752:and
711:and
661:CISH
657:CBLB
609:CD28
589:cGMP
456:CART
384:and
368:and
313:CD19
68:news
37:for
3093:PMC
3085:doi
3044:PMC
3036:doi
2995:PMC
2987:doi
2975:314
2938:PMC
2930:doi
2926:114
2889:PMC
2881:doi
2840:PMC
2832:doi
2820:298
2783:doi
2742:PMC
2734:doi
2690:PMC
2682:doi
2641:PMC
2633:doi
2629:117
2592:PMC
2584:doi
2543:PMC
2535:doi
2473:PMC
2465:doi
2461:212
2424:PMC
2416:doi
2367:PMC
2359:doi
2355:212
2318:PMC
2310:doi
2306:112
2269:PMC
2261:doi
2220:PMC
2212:doi
2208:115
2171:PMC
2163:doi
2122:PMC
2114:doi
2073:PMC
2065:doi
2021:PMC
2013:doi
1959:doi
1915:PMC
1905:doi
1811:doi
1799:534
1766:PMC
1758:doi
1754:127
1647:PMC
1639:doi
1627:348
1553:PMC
1545:doi
1504:PMC
1496:doi
1442:or
1339:45%
1315:67%
1286:30
1267:27%
1261:GD2
1245:67%
1236:ALL
1223:88%
1214:ALL
1201:80%
1180:90%
1171:ALL
1149:ALL
1127:CLL
1067:33%
1020:22%
999:40%
978:38%
958:48%
937:56%
916:46%
896:34%
875:55%
723:or
611:or
537:CD3
522:).
454:);
428:FDA
340:FDA
270:CD4
266:CD8
192:ACT
151:by
3149::
3101:.
3091:.
3081:20
3079:.
3075:.
3052:.
3042:.
3030:.
3026:.
3003:.
2993:.
2985:.
2973:.
2969:.
2946:.
2936:.
2924:.
2920:.
2897:.
2887:.
2877:23
2875:.
2871:.
2848:.
2838:.
2830:.
2818:.
2814:.
2791:.
2779:16
2777:.
2773:.
2750:.
2740:.
2730:30
2728:.
2724:.
2712:^
2698:.
2688:.
2678:20
2676:.
2672:.
2649:.
2639:.
2627:.
2623:.
2600:.
2590:.
2578:.
2574:.
2551:.
2541:.
2531:12
2529:.
2525:.
2481:.
2471:.
2459:.
2455:.
2432:.
2422:.
2414:.
2402:.
2398:.
2375:.
2365:.
2353:.
2349:.
2326:.
2316:.
2304:.
2300:.
2277:.
2267:.
2257:35
2255:.
2251:.
2228:.
2218:.
2206:.
2202:.
2179:.
2169:.
2159:17
2157:.
2153:.
2130:.
2120:.
2110:13
2108:.
2104:.
2081:.
2071:.
2061:22
2059:.
2055:.
2043:^
2029:.
2019:.
2009:34
2007:.
2003:.
1982:.
1965:.
1955:75
1953:.
1949:.
1923:.
1913:.
1901:22
1899:.
1895:.
1870:.
1849:.
1845:.
1825:.
1817:.
1809:.
1797:.
1774:.
1764:.
1752:.
1748:.
1736:^
1719:.
1708:^
1691:.
1669:^
1655:.
1645:.
1637:.
1625:.
1621:.
1575:^
1561:.
1551:.
1539:.
1535:.
1512:.
1502:.
1492:31
1490:.
1486:.
1466:.
1454:.
1430:,
1415:,
1411:,
1383:.
1336:11
1264:11
1242:21
1220:16
1198:15
1177:30
1086:11
996:57
975:13
955:31
934:93
913:13
893:86
872:20
796:,
792:,
788:,
784:,
776:,
772:,
768:,
764:,
623:.
514:,
510:,
490:,
486:,
474:,
470:,
466:,
462:,
446:,
380:,
376:,
364:,
360:,
356:,
331:.
319:.
206:,
56:.
3109:.
3087::
3060:.
3038::
3032:3
3011:.
2989::
2981::
2954:.
2932::
2905:.
2883::
2856:.
2834::
2826::
2799:.
2785::
2758:.
2736::
2706:.
2684::
2657:.
2635::
2608:.
2586::
2580:6
2559:.
2537::
2510:.
2489:.
2467::
2440:.
2418::
2410::
2404:8
2383:.
2361::
2334:.
2312::
2285:.
2263::
2236:.
2214::
2187:.
2165::
2138:.
2116::
2089:.
2067::
2037:.
2015::
1973:.
1961::
1931:.
1907::
1880:.
1833:.
1813::
1805::
1782:.
1760::
1730:.
1702:.
1663:.
1641::
1633::
1569:.
1547::
1541:2
1520:.
1498::
1312:6
1155:5
1133:3
1111:1
1089:–
1064:9
1042:–
1039:1
1017:9
679:(
190:(
178:)
172:(
167:)
163:(
145:.
107:)
103:(
93:·
86:·
79:·
72:·
46:.
Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.