405:(formerly RG6013) is an IgG derivative containing H-chain heterodimerization motifs, which was combined with the common light chain approach to prevent L-chain mispairing issues. With a bivalent composition, emicizumab brings two protein antigens together into one complex. Factor IXa and Factor X in the coagulation cascade are the cognate antigens which are bound by RG6013. These two factors are brought together by coagulation factor VIIIa in a healthy individual, while patients with bleeding disorder hemophilia A do not have VIIIa. Current treatment of this disorder is to supplement the patients with FVIII to reduce bleeding complications. But FVIII can be recognized as a foreign protein in these patients due to the absence of this protein and thus an immune response will be generated against this protein. Besides, FVIII has a short half-life (less than 15 hours) and thus is cleared rapidly. However, the humanized BsAb has lower immunogenicity and long serum half-life compared with FVIII and thus provide a better treatment for hemophilia.
454:
total of eight more bispecific antibody drugs have since been approved by the US FDA: blinatumomab, emacizumab, amivantamab, tebentafusp, faricimab, teclistamab, mosunetuzumab, epcoritamab, glofitamab. Among the bsAb programs currently under development, the combination of CD3 and tumor surface targets are the most popular targets pairs. Other popular targets are CD3, HER2, PD-1, PD-L1, EGFR, CTLA-4, etc., which as well as immune targets of PD-1, PD-L1, BCMA, CD47, CTLA-4, LAG-3, 4 -1BB. Additionally, with the approval of the several new bsAb since 2022, and new mechanisms for improving efficacy like development of hetero-dimer bispecific molecules, several additional possibilities of target pairs have emerged.
92:
2331:
370:(Vectibix), both of which are directed against HER1. However, cancer cells can switch to a different pathway to escape the growth inhibition generated by blocking one signaling pathway. To improve the therapeutic efficacy, simultaneously interfering/blocking of two (or more) RTK signaling pathways, achieved through the mediation of BsAb to inactivate either the RTKs or their ligand, reduces the possibility of the escape mechanisms adopted by the tumor cells.
160:
254:
2530:
2542:
541:
58:. Naturally occurring antibodies typically only target one antigen. BsAbs can be manufactured in several structural formats. BsAbs can be designed to recruit and activate immune cells, to interfere with receptor signaling and inactivate signaling ligands, and to force association of protein complexes. BsAbs have been explored for
466:, which means the Fc region could cause detrimental downstream immune responses caused by cells that are activated by Fc receptors. The therapeutic use of BsAbs as a whole is still largely in development, with many clinical trials currently ongoing that are determining the efficacy and safety of BsAbs for treatment.
440:
lower than with ordinary antibodies. For non-IgG-like BsAbs, their smaller size allows them to reach antigens usually unavailable to conventional antibodies. In the case of Ebola vaccines, this method allows the antibody to target intracellular targets not usually accessible by traditional monoclonal
474:
Bispecific antibodies have a wide variety of applications in diagnosis and therapy. BsAbs can be combined with HRPO, can be used in pre-targeting strategies, and can be used to provide better imaging for early detection in diagnosis. To treat cancer, BsAbs can target immune cells precisely, help and
453:
Currently, nine bsAb drugs have been approved by the US FDA / EMA and over 180 are currently in clinical trials. The first bispecific antibody to gain regulatory approval, blinatumomab, targets CD19 on B cells and CD3 on T cells, leading to the activation of T cells and the destruction of B cells. A
206:
S linker to connect two ScFvs-one CD3 antibody ScFv and one tumor-associated antigen (TAA) or tumor-specific ScFv-to redirect T cells to cancer cells for target killing. Other platforms include tetravalent antiparallel structure (TandAbs) and VH only (Bi-Nanobody). The TandAb platform is formed by a
392:
of the viral coat and enter the cell with the virus. These outer regions are cleaved in the viral endosome, revealing the inner variable regions that then bind to both the virus and internal receptors in the endosome. Blocking the interaction between the virus and endosomal proteins prevents viral
475:
reactive the immune cells, fine-tune the fate and function of immune cells, improve the tolerance of immune cells, and promote the return to immune homeostasis. BsAbs can also be applied to treat other diseases, including hemophilia A, diabetes, Alzeimer's disease, and ophthalmological diseases.
444:
Additionally, targeting more than one molecule can be useful to circumvent the regulation of parallel pathways and avoid resistance to the treatment. Binding or blocking multiple targets in a pathway can be beneficial to stopping disease, as most conditions have complicated multifaceted effects
219:. The Bi-Nanobody platform forms multi-specific binding through the connection between the VH regions of two or more antibody molecules. The products that are designed based on this platform are small molecules and these small molecules have high stability and better tissue permeability
163:
The "knobs into holes" approach for manufacturing IgG-like bsMabs is shown on the left, while a diagram depicting the DVD-Ig format is on the right. The red dot indicates a possible site for introducing mutations in the heavy chain. Blue and yellow correspond to separate monoclonal
338:
233:
Preparation of expression system – An expression system is chosen and prepared for antibody expression. Frequently used expression systems for therapeutic bispecific antibodies are mammalian cells, such as CHO cells, as they are effective in performing complex post-translational
173:
in the heavy chain from one mAb, and a mutation for a small amino acid in the other mAb's heavy chain. This allows the target heavy chains (and their corresponding light chains) to fit together better, and makes the production of BsAbs more reliable.
83:(scFv) was invented by the Huston team to minimize the refolding problems, which contains the incorrect domain pairing or aggregation of two-chain species. In 1996, the BsAbs became more developed when the knobs-into-holes technology emerged.
70:
The original concept of BsAbs was proposed by
Nisonoff and his collaborators in the 1960s, including the first idea of antibody architecture and other findings. In 1975, the problem of producing pure antibodies was solved by the creation of
115:
There are many formats of BsAbs, but the two main categories are IgG-like and non-IgG-like. The main types of manufacturing methods are quadromas, chemical conjugation, and genetic recombination, and each method results in a unique format.
445:
throughout the body. Together with combination therapies, BsAbs are being used more and more to treat certain types of cancers, as, over time, some tumors develop resistances to checkpoint inhibitors and/or co-stimulatory molecules.
168:
However, the quadroma method relies on random chance to form usable BsAb, and can be inefficient. Another method for manufacturing IgG-like BsAb is called "knobs into holes," and relies on introducing a mutation for a large
545:
237:
Transfection and protein production – Either via stable or transient transfection, genetic information of the desired bispecific antibodies is inserted into the expression system, which consequently expresses the proteins
1438:
Kipriyanov SM, Moldenhauer G, Schuhmacher J, Cochlovius B, Von der Lieth CW, Matys ER, Little M (October 1999). "Bispecific tandem diabody for tumor therapy with improved antigen binding and pharmacokinetics".
1742:
Kitazawa T, Igawa T, Sampei Z, Muto A, Kojima T, Soeda T, et al. (October 2012). "A bispecific antibody to factors IXa and X restores factor VIII hemostatic activity in a hemophilia A model".
241:
Protein purification – Steps to isolate and enrich bispecific antibodies are taken. This can include several purification processes, such as protein A affinity chromatography or peptide tagging.
1949:"Identification of sequences common to more than one therapeutic target to treat complex diseases: simulating the high variance in sequence interactivity evolved to modulate robust phenotypes"
207:
tetravalent antibody molecule containing two binding sites for each of two antigens. In this platform, the reverse pairing of two peptide chains forms a homodimer molecule. As an example, AFM
1639:
Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL (January 1987). "Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene".
230:
Genetic engineering and cloning – Different monoclonal antibodies or antibody fragments are fused. Recombinant DNA technology is applied to generate one single, bispecific antibody.
244:
Antibody characterization – Characterization and quality control conclude the production process. Effector functions, stability and binding specificity are examined at this stage.
1847:
Bargou R, Leo E, Zugmaier G, Klinger M, Goebeler M, Knop S, et al. (August 2008). "Tumor regression in cancer patients by very low doses of a T cell-engaging antibody".
2170:
223:. Even though non-IgG-like BsAbs have low molecular weight and thus high tumor tissue permeability, their half-life is relatively short and they require multiple doses.
1399:"Introducing antigen-binding sites in structural loops of immunoglobulin constant domains: Fc fragments with engineered HER2/neu-binding sites and antibody properties"
2283:
2115:
420:
because the Fab regions are already used for binding the tumor cells, and this type of cell does not have Fc receptors. Bispecific antibodies also have a higher
327:
226:
Despite the considerable differences between the various types and formats of bispecific antibodies, their manufacturing processes correspond in several steps:
362:(IGF). The RTKs are therefore preferred targets in cancer therapy. Although monospecific RTK-targeting IgGs have already been available in the market, such as
1258:"Preferential species-restricted heavy/light chain pairing in rat/mouse quadromas. Implications for a single-step purification of bispecific antibodies"
939:"Protein engineering of antibody binding sites: recovery of specific activity in an anti-digoxin single-chain Fv analogue produced in Escherichia coli"
1787:"Identification and multidimensional optimization of an asymmetric bispecific IgG antibody mimicking the function of factor VIII cofactor activity"
2069:
2050:
148:
pair is from a unique mAb. The Fc region made from the two heavy chains forms the third binding site. These BsAbs are often manufactured with the
326:. Since the Fc region is still intact, this allows for the BsAb to trigger common immune responses when recognized by an Fc receptor, such as
286:
cell) to be destroyed. It is possible to observe the bridging effect that BsAbs have on T cell/cancer cell interactions using label-free
2276:
274:
The binding of a BsAb to its target antigens can lead to a variety of effects. The most widely used application of this approach is in
2393:
1042:
Wang, Qiong; Chen, Yiqun; Park, Jaeyoung; Liu, Xiao; Hu, Yifeng; Wang, Tiexin; McFarland, Kevin; Betenbaugh, Michael J. (2019-08-02).
331:
303:
996:
Merchant AM, Zhu Z, Yuan JQ, Goddard A, Adams CW, Presta LG, Carter P (July 1998). "An efficient route to human bispecific IgG".
528:
2567:
737:
Nisonoff A, Wissler FC, Lipman LN (December 1960). "Properties of the major component of a peptic digest of rabbit antibody".
2562:
2383:
2269:
1476:"A tetravalent bispecific TandAb (CD19/CD3), AFM11, efficiently recruits T cells for the potent lysis of CD19(+) tumor cells"
556:
187:
133:
80:
182:
There are other BsAbs that lack an Fc region entirely, and thus leads to relatively simple design strategies. These include
385:
2520:
791:
Nisonoff A, Rivers MM (May 1961). "Recombination of a mixture of univalent antibody fragments of different specificity".
500:
829:
Köhler G, Milstein C (August 1975). "Continuous cultures of fused cells secreting antibody of predefined specificity".
2405:
524:
359:
199:
145:
141:
104:
2177:
75:, and the new era of monoclonal antibodies (MoAbs) came. In 1983, Milstein and Cuello created hybrid-hybridoma (
2347:
2339:
2255:
355:
129:
1158:
Müller D, Kontermann RE (April 2010). "Bispecific antibodies for cancer immunotherapy: Current perspectives".
1575:
516:
496:
2388:
2318:
262:
137:
96:
2261:
2363:
183:
140:, as they have three unique binding sites on the antibody: the two Fab regions, and the Fc region. Each
100:
2091:
1856:
1798:
1698:
1648:
1397:
Wozniak-Knopp G, Bartl S, Bauer A, Mostageer M, Woisetschläger M, Antes B, et al. (April 2010).
950:
937:
Huston JS, Levinson D, Mudgett-Hunter M, Tai MS, Novotný J, Margolies MN, et al. (August 1988).
892:
838:
746:
413:
275:
153:
72:
59:
2330:
1785:
Sampei Z, Igawa T, Soeda T, Okuyama-Nishida Y, Moriyama C, Wakabayashi T, et al. (2013-02-28).
91:
2439:
2293:
437:
319:
125:
108:
1685:
Wec AZ, Nyakatura EK, Herbert AS, Howell KA, Holtsberg FW, Bakken RR, et al. (October 2016).
1362:
Baeuerle PA, Reinhardt C (June 2009). "Bispecific T-cell engaging antibodies for cancer therapy".
211:
is based on the TandAbs platform and targets both CD3 and CD19 to achieve therapeutic effects. AFM
2251:
2225:
1929:
1880:
1767:
1621:
1287:
1183:
1021:
916:
883:
Milstein C, Cuello AC (October 1983). "Hybrid hybridomas and their use in immunohistochemistry".
862:
770:
1898:
Weiner LM, Holmes M, Richeson A, Godwin A, Adams GP, Hsieh-Ma ST, et al. (September 1993).
17:
2131:"A review of bispecific antibodies and antibody constructs in oncology and clinical challenges"
2457:
2217:
2152:
2109:
2031:
1980:
1921:
1872:
1826:
1759:
1724:
1664:
1613:
1556:
1505:
1474:
Reusch U, Duell J, Ellwanger K, Herbrecht C, Knackmuss SH, Fucek I, et al. (2015-05-04).
1456:
1420:
1379:
1341:
1279:
1235:
1175:
1137:
1083:
1065:
1013:
978:
908:
854:
808:
762:
719:
659:
615:
433:
417:
342:
287:
2449:
2297:
2207:
2142:
2021:
2011:
1970:
1960:
1911:
1864:
1816:
1806:
1751:
1714:
1706:
1656:
1605:
1546:
1536:
1495:
1487:
1448:
1410:
1371:
1331:
1321:
1269:
1225:
1217:
1167:
1127:
1117:
1073:
1055:
1005:
968:
958:
900:
846:
800:
754:
709:
699:
649:
605:
595:
492:
337:
299:
295:
1900:"Binding and cytotoxicity characteristics of the bispecific murine monoclonal antibody 2B1"
1310:"Bispecific Antibodies as a Development Platform for New Concepts and Treatment Strategies"
2546:
425:
195:
1687:"A "Trojan horse" bispecific-antibody strategy for broad protection against ebolaviruses"
1257:
1860:
1802:
1702:
1652:
954:
896:
842:
750:
380:, a study has shown that a DVD-Ig antibody can be used to prevent viral escape from the
2534:
2026:
1999:
1975:
1948:
1821:
1786:
1719:
1686:
1551:
1524:
1500:
1475:
1336:
1309:
1230:
1205:
1132:
1105:
1078:
1043:
714:
687:
610:
583:
463:
323:
307:
191:
1525:"Nanobodies and Nanobody-Based Human Heavy Chain Antibodies As Antitumor Therapeutics"
973:
938:
253:
2556:
2497:
2423:
2229:
2212:
2191:
2147:
2130:
1171:
1106:"Fc Engineering for Developing Therapeutic Bispecific Antibodies and Novel Scaffolds"
804:
511:. Catumaxomab was withdrawn from the European market in 2017 for commercial reasons.
388:. Researchers developed DVD-Igs where the outer variable regions bind to the surface
294:, one of the first trifunctional antibodies approved for therapeutic use, binds both
136:, except the two Fab sites bind different antigens. The most common types are called
1933:
1884:
1771:
1291:
1187:
1025:
774:
1625:
1596:
Yarden Y, Sliwkowski MX (February 2001). "Untangling the ErbB signalling network".
920:
866:
508:
484:
389:
159:
1491:
1375:
758:
1811:
654:
637:
341:
Example of cancer cells being killed cytotoxic T-cells. Imaged with a label-free
2245:
1916:
1899:
512:
367:
311:
291:
258:
2529:
1274:
1206:"Bispecific antibodies for cancer therapy: the light at the end of the tunnel?"
943:
Proceedings of the
National Academy of Sciences of the United States of America
1965:
704:
600:
504:
402:
374:
315:
170:
1541:
1415:
1398:
1122:
1069:
2507:
2482:
2477:
1868:
1710:
1660:
963:
429:
421:
363:
279:
2221:
2156:
2035:
1984:
1876:
1830:
1763:
1728:
1617:
1560:
1509:
1460:
1452:
1424:
1383:
1345:
1239:
1221:
1179:
1141:
1087:
812:
766:
723:
663:
619:
2171:"Removab: Withdrawal of the marketing authorisation in the European Union"
1925:
1668:
1283:
1017:
982:
912:
858:
2502:
2375:
2016:
1326:
1060:
381:
198:
of two antibodies. The furthest developed of these newer formats are the
149:
76:
51:
1009:
507:, which targets clotting factors IXa and X, is used in the treatment of
2472:
2467:
2462:
377:
55:
47:
43:
2129:
Suurs FV, Lub-de Hooge MN, de Vries EG, de Groot DJ (September 2019).
2070:"Bispecific Antibodies: An Area of Research and Clinical Applications"
2051:"Bispecific Antibodies: An Area of Research and Clinical Applications"
350:
Interfering with receptor signaling and inactivating signaling ligands
2492:
2487:
1998:
Koustas E, Sarantis P, Papavassiliou AG, Karamouzis MV (April 2020).
1609:
904:
850:
283:
2000:"The Resistance Mechanisms of Checkpoint Inhibitors in Solid Tumors"
1755:
550:
107:(bottom row). Blue and yellow parts distinguish parts from separate
523:
receptors, for adult patients with locally advanced or metastatic
520:
428:
relatively weakly. The effective dose is around 0.01 mg·m·d (
336:
158:
488:
2265:
584:"Bispecific Antibodies: From Research to Clinical Application"
582:
Ma J, Mo Y, Tang M, Shen J, Qi Y, Zhao W, et al. (2021).
1256:
Lindhofer H, Mocikat R, Steipe B, Thierfelder S (July 1995).
310:. The Fc region additionally binds to a cell that expresses
1576:"Bispecific antibody production – a comprehensive overview"
483:
Three bispecific antibodies are presently in clinical use.
354:
The growth of tumor cells can be simulated or modulated by
186:, consisting of only the Fab regions, and various types of
2248:
entry in the public domain NCI Dictionary of Cancer Terms
2068:
Research, Center for Drug
Evaluation and (2023-08-02).
2049:
Research, Center for Drug
Evaluation and (2023-08-02).
46:
that can simultaneously bind to two different types of
278:, where BsAbs are engineered to simultaneously bind a
188:
bivalent and trivalent single-chain variable fragments
2518:
2448:
2432:
2416:
2384:
Single-chain variable fragment / di-scFv / tri-scFv
2374:
2338:
2304:
257:The mechanism of action of a BsAb, exemplified by
1044:"Design and Production of Bispecific Antibodies"
393:escape from the endosome and further infection.
215:showed dose-dependent inhibition of Raji tumors
2092:"Popular Targets for Bispecific Antibody Drugs"
358:(RTKs), including members of the Her family or
1104:Liu H, Saxena A, Sidhu SS, Wu D (2017-01-01).
688:"Bispecific antibodies and their applications"
409:Advantages over ordinary monoclonal antibodies
2277:
416:with ordinary monoclonal antibodies does not
328:antibody-dependent cell-mediated cytotoxicity
261:, representing the first approved bispecific
8:
1251:
1249:
686:Fan G, Wang Z, Hao M, Li J (December 2015).
2114:: CS1 maint: numeric names: authors list (
1403:Protein Engineering, Design & Selection
1357:
1355:
1314:International Journal of Molecular Sciences
2284:
2270:
2262:
1523:Bannas P, Hambach J, Koch-Nolte F (2017).
1153:
1151:
87:Structural types and manufacturing methods
62:, drug delivery, and Alzheimer's disease.
2254:at the U.S. National Library of Medicine
2211:
2146:
2025:
2015:
1974:
1964:
1915:
1842:
1840:
1820:
1810:
1718:
1550:
1540:
1499:
1414:
1335:
1325:
1273:
1229:
1199:
1197:
1131:
1121:
1077:
1059:
972:
962:
713:
703:
653:
609:
599:
424:potential, and bind to antigens that are
270:Recruiting and activating of immune cells
636:Kontermann RE, Brinkmann U (July 2015).
397:Forcing association of protein complexes
252:
90:
2525:
793:Archives of Biochemistry and Biophysics
563:
2107:
1598:Nature Reviews. Molecular Cell Biology
1308:Yang F, Wen W, Qin W (December 2016).
95:Three types of bispecific antibodies:
2085:
2083:
1680:
1678:
1574:Schofield, Desmond (August 3, 2023).
1303:
1301:
1099:
1097:
7:
692:Journal of Hematology & Oncology
681:
679:
677:
675:
673:
631:
629:
577:
575:
573:
571:
569:
567:
531:(EGFR) exon 20 insertion mutations.
124:This format retains the traditional
2394:Small modular immunopharmaceutical
458:Problems and current disadvantages
25:
332:complement-dependent cytotoxicity
2540:
2528:
2329:
2213:10.1158/2159-8290.CD-NB2021-0351
2148:10.1016/j.pharmthera.2019.04.006
1172:10.2165/11530960-000000000-00000
544: This article incorporates
539:
529:epidermal growth factor receptor
18:Bispecific monoclonal antibodies
2135:Pharmacology & Therapeutics
384:. Ebolaviruses infect cells by
2246:Bispecific monoclonal antibody
557:U.S. National Cancer Institute
495:, is used in the treatment of
449:Current Scenario of bsAb drugs
81:single-chain variable fragment
32:bispecific monoclonal antibody
1:
2206:(7): 1604.1–1604. July 2021.
1492:10.1080/19420862.2015.1029216
1376:10.1158/0008-5472.CAN-09-0547
759:10.1126/science.132.3441.1770
386:receptor-mediated endocytosis
373:In addition, in working with
1812:10.1371/journal.pone.0057479
1441:Journal of Molecular Biology
805:10.1016/0003-9861(61)90296-x
655:10.1016/j.drudis.2015.02.008
501:acute lymphoblastic leukemia
2090:krishgen2023 (2023-03-24).
1917:10.4049/jimmunol.151.5.2877
462:IgG-like antibodies can be
436:per day), which is several
200:bi-specific T-cell engagers
79:) technology. In 1988, the
2584:
1275:10.4049/jimmunol.155.1.219
552:Dictionary of Cancer Terms
525:non-small cell lung cancer
360:insulin-like growth factor
105:bi-specific T-cell engager
2327:
2178:European Medicines Agency
1966:10.1186/s12864-015-1727-6
1204:Chames P, Baty D (2009).
705:10.1186/s13045-015-0227-0
601:10.3389/fimmu.2021.626616
202:(BiTEs), which uses the G
2352:fragment / Fab' fragment
2256:Medical Subject Headings
1542:10.3389/fimmu.2017.01603
1123:10.3389/fimmu.2017.00038
356:receptor tyrosine kinase
190:(ScFvs). There are also
138:trifunctional antibodies
1947:Varela MA (July 2015).
1869:10.1126/science.1158545
1711:10.1126/science.aag3267
1661:10.1126/science.3798106
1529:Frontiers in Immunology
1110:Frontiers in Immunology
1031:(subscription required)
964:10.1073/pnas.85.16.5879
926:(subscription required)
872:(subscription required)
818:(subscription required)
780:(subscription required)
638:"Bispecific antibodies"
588:Frontiers in Immunology
517:epidermal growth factor
497:Philadelphia chromosome
128:(mAb) structure of two
2568:Immunomodulating drugs
2389:Single-domain antibody
2319:Trifunctional antibody
2192:"Amivantamab OK'd for
1453:10.1006/jmbi.1999.3156
1416:10.1093/protein/gzq005
1222:10.4161/mabs.1.6.10015
546:public domain material
418:activate T-lymphocytes
346:
266:
263:trifunctional antibody
184:chemically linked Fabs
165:
112:
97:trifunctional antibody
2563:Monoclonal antibodies
2498:Kunitz domain peptide
2364:Chemically linked Fab
2294:monoclonal antibodies
2252:Bispecific+antibodies
1904:Journal of Immunology
1262:Journal of Immunology
441:antibody treatments.
340:
282:cell and a target (a
256:
162:
109:monoclonal antibodies
101:chemically linked Fab
94:
2017:10.3390/biom10050666
1327:10.3390/ijms18010048
1061:10.3390/antib8030043
998:Nature Biotechnology
642:Drug Discovery Today
414:Cancer immunotherapy
276:cancer immunotherapy
73:hybridoma technology
60:cancer immunotherapy
2096:Krishgen Biosystems
1861:2008Sci...321..974B
1803:2013PLoSO...857479S
1703:2016Sci...354..350W
1653:1987Sci...235..177S
1010:10.1038/nbt0798-677
955:1988PNAS...85.5879H
897:1983Natur.305..537M
843:1975Natur.256..495K
751:1960Sci...132.1770N
745:(3441): 1770–1771.
479:BsAbs on the market
438:orders of magnitude
320:natural killer cell
249:Mechanism of action
126:monoclonal antibody
66:Development history
42:) is an artificial
347:
267:
166:
113:
27:Artificial protein
2516:
2515:
2458:Affibody molecule
2450:Antibody mimetics
2376:Variable fragment
2298:antibody mimetics
1855:(5891): 974–977.
1750:(10): 1570–1574.
1697:(6310): 350–354.
1647:(4785): 177–182.
1370:(12): 4941–4944.
949:(16): 5879–5883.
891:(5934): 537–540.
837:(5517): 495–497.
515:, which targets
434:body surface area
432:per square meter
343:live cell imaging
300:cytotoxic T cells
288:live cell imaging
50:or two different
16:(Redirected from
2575:
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2200:Cancer Discovery
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2019:
1995:
1989:
1988:
1978:
1968:
1944:
1938:
1937:
1919:
1910:(5): 2877–2886.
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993:
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905:10.1038/305537a0
880:
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851:10.1038/256495a0
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788:
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778:
734:
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707:
683:
668:
667:
657:
633:
624:
623:
613:
603:
579:
560:
543:
542:
499:negative B cell
487:, which targets
196:variable domains
152:, or the hybrid
21:
2583:
2582:
2578:
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2190:
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2100:
2098:
2089:
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2067:
2066:
2062:
2048:
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1997:
1996:
1992:
1946:
1945:
1941:
1897:
1896:
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1838:
1784:
1783:
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1756:10.1038/nm.2942
1744:Nature Medicine
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1364:Cancer Research
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411:
401:As an example,
399:
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308:adenocarcinomas
272:
251:
214:
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192:fusion proteins
180:
122:
89:
68:
28:
23:
22:
15:
12:
11:
5:
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2406:T-cell engager
2396:
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2371:
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2368:
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2342:
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2328:
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2324:
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2322:
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2308:
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2305:Whole antibody
2302:
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2291:
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2274:
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2259:
2249:
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2240:External links
2238:
2236:
2235:
2196:-Mutant NSCLC"
2183:
2162:
2121:
2079:
2060:
2041:
1990:
1939:
1890:
1836:
1777:
1734:
1674:
1631:
1604:(2): 127–137.
1588:
1566:
1515:
1486:(3): 584–604.
1466:
1430:
1409:(4): 289–297.
1389:
1351:
1297:
1268:(1): 219–225.
1245:
1216:(6): 539–547.
1193:
1147:
1093:
1034:
1004:(7): 677–681.
988:
929:
875:
821:
799:(2): 460–462.
783:
729:
669:
648:(7): 838–847.
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366:(Erbitux) and
351:
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324:dendritic cell
271:
268:
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242:
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235:
234:modifications.
231:
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194:mimicking the
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2433:Intracellular
2431:
2425:
2424:Microantibody
2422:
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2417:Smaller units
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2180:. 2017-07-10.
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527:(NSCLC) with
526:
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396:
394:
391:
390:glycoproteins
387:
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365:
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344:
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329:
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143:
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132:arms and one
131:
127:
119:
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93:
86:
84:
82:
78:
74:
65:
63:
61:
57:
53:
49:
45:
41:
37:
33:
19:
2399:
2398:
2357:
2356:
2340:Fab fragment
2312:
2311:
2203:
2199:
2193:
2186:
2165:
2138:
2134:
2124:
2099:. Retrieved
2095:
2073:
2063:
2054:
2044:
2010:(5): 66–82.
2007:
2004:Biomolecules
2003:
1993:
1956:
1953:BMC Genomics
1952:
1942:
1907:
1903:
1893:
1852:
1848:
1794:
1790:
1780:
1747:
1743:
1737:
1694:
1690:
1644:
1640:
1634:
1601:
1597:
1591:
1581:December 11,
1579:. Retrieved
1569:
1532:
1528:
1518:
1483:
1479:
1469:
1447:(1): 41–56.
1444:
1440:
1433:
1406:
1402:
1392:
1367:
1363:
1317:
1313:
1265:
1261:
1213:
1209:
1166:(2): 89–98.
1163:
1159:
1113:
1109:
1051:
1047:
1037:
1001:
997:
991:
946:
942:
932:
888:
884:
878:
834:
830:
824:
796:
792:
786:
742:
738:
732:
695:
691:
645:
641:
591:
587:
551:
538:
509:hemophilia A
485:Blinatumomab
482:
473:
470:Applications
461:
452:
443:
412:
400:
372:
353:
312:Fc receptors
273:
238:accordingly.
225:
220:
216:
181:
178:Non-IgG-like
167:
123:
114:
69:
54:on the same
39:
35:
31:
29:
2292:Engineered
2141:: 103–119.
513:Amivantamab
464:immunogenic
368:panitumumab
345:microscope.
292:Catumaxomab
259:catumaxomab
164:antibodies.
156:, method.
146:light chain
2557:Categories
2400:bispecific
2358:bispecific
2313:bispecific
2101:2023-09-16
1959:(1): 530.
1048:Antibodies
594:: 626616.
535:References
519:(EGF) and
505:Emicizumab
430:milligrams
403:emicizumab
375:Ebolavirus
316:macrophage
306:on human
171:amino acid
2508:nanoCLAMP
2483:Anticalin
2478:Alphabody
2440:Intrabody
2230:235334950
1320:(1): 48.
1070:2073-4468
1054:(3): 43.
426:expressed
422:cytotoxic
364:cetuximab
314:, like a
280:cytotoxic
154:hybridoma
134:Fc region
2547:Medicine
2503:Monobody
2222:34083225
2157:31028837
2110:cite web
2036:32344837
1985:26187740
1934:30441206
1885:22628198
1877:18703743
1831:23468998
1791:PLOS ONE
1772:13125020
1764:23023498
1729:27608667
1618:11252954
1561:29213270
1535:: 1603.
1510:25875246
1461:10512714
1425:20150180
1384:19509221
1346:28036020
1292:34289723
1240:20073127
1188:27797190
1180:20199124
1160:BioDrugs
1142:28184223
1088:31544849
1026:41622760
813:13729244
775:19267292
767:13729245
724:26692321
664:25728220
620:34025638
382:endosome
378:vaccines
150:quadroma
120:IgG-like
77:quadroma
52:epitopes
2535:Biology
2521:Portals
2473:Affitin
2468:Affimer
2463:Affilin
2027:7277892
1976:4506634
1926:8103070
1857:Bibcode
1849:Science
1822:3585358
1799:Bibcode
1720:5647781
1699:Bibcode
1691:Science
1669:3798106
1649:Bibcode
1641:Science
1626:4235503
1552:5702627
1501:4622993
1337:5297683
1284:7602098
1231:2791310
1133:5266686
1079:6783844
1018:9661204
983:3045807
951:Bibcode
921:4264730
913:6137772
893:Bibcode
867:4161444
859:1172191
839:Bibcode
747:Bibcode
739:Science
715:4687327
698:: 130.
611:8131538
503:(ALL).
221:in vivo
217:in vivo
56:antigen
48:antigen
44:protein
2493:DARPin
2488:Avimer
2348:F(ab')
2258:(MeSH)
2228:
2220:
2155:
2034:
2024:
1983:
1973:
1932:
1924:
1883:
1875:
1829:
1819:
1770:
1762:
1727:
1717:
1667:
1624:
1616:
1559:
1549:
1508:
1498:
1459:
1423:
1382:
1344:
1334:
1290:
1282:
1238:
1228:
1186:
1178:
1140:
1130:
1116:: 38.
1086:
1076:
1068:
1024:
1016:
981:
974:281868
971:
919:
911:
885:Nature
865:
857:
831:Nature
811:
773:
765:
722:
712:
662:
618:
608:
284:tumour
2226:S2CID
2174:(PDF)
1930:S2CID
1881:S2CID
1768:S2CID
1622:S2CID
1288:S2CID
1184:S2CID
1022:S2CID
917:S2CID
863:S2CID
771:S2CID
548:from
304:EpCAM
142:heavy
36:BsMAb
2296:and
2218:PMID
2194:EGFR
2153:PMID
2116:link
2032:PMID
1981:PMID
1922:PMID
1873:PMID
1827:PMID
1760:PMID
1725:PMID
1665:PMID
1614:PMID
1583:2023
1557:PMID
1506:PMID
1480:mAbs
1457:PMID
1421:PMID
1380:PMID
1342:PMID
1280:PMID
1236:PMID
1210:mAbs
1176:PMID
1138:PMID
1084:PMID
1066:ISSN
1014:PMID
979:PMID
909:PMID
855:PMID
809:PMID
763:PMID
720:PMID
660:PMID
616:PMID
491:and
489:CD19
302:and
144:and
103:and
40:BsAb
2208:doi
2143:doi
2139:201
2074:FDA
2055:FDA
2022:PMC
2012:doi
1971:PMC
1961:doi
1912:doi
1908:151
1865:doi
1853:321
1817:PMC
1807:doi
1752:doi
1715:PMC
1707:doi
1695:354
1657:doi
1645:235
1606:doi
1547:PMC
1537:doi
1496:PMC
1488:doi
1449:doi
1445:293
1411:doi
1372:doi
1332:PMC
1322:doi
1270:doi
1266:155
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