Journal of Immunology Research / 2019 / Article / Tab 1

Review Article

Immunoglobulin Gamma-Like Therapeutic Bispecific Antibody Formats for Tumor Therapy

Table 1

Immunoglobulin gamma-like bispecific antibody formats.

FormatCompanyPublication dateMoleculeTargetsFunctionIndicationClinical trialsCompanyPublication number

(A) Immunoglobulin gamma-like asymmetric bispecific antibodies
Knobs-into-holes (KiH)Genentech06 September 1996(Including in the CrossMAb)
CrossMAbRoche02 July 2009RG-6026CD3×CD20T cell recruitmentRelapsed or refractory non-Hodgkin’s lymphomaIRocheWO2016020309 A1
RG-7221Angiopoietin 2×VEGF2-ligand inactivationColorectal cancerIIRocheWO2011117329 A1
Solid tumorsI
RG-7386FAP×DR5Tumor site-specific cell apoptosisSolid tumorsIRocheWO2014161845 A1
RG-7716Angiopoietin-2×VEGF2-ligand inactivationDiabetic macular edema, wet age-related macular degenerationIIRocheUS20170260265 A1
RG-7802CEA×CD3T cell recruitmentSolid tumorsIRocheWO2013026833 A1
RG-7828CD3×CD20T cell recruitmentChronic lymphocytic leukemia, non-Hodgkin’s lymphomaIGenentechWO2016204966 A1
Triomab quadromaFresenius Biotech, TriOn Pharma14 December 1995CatumaxomabEpCAM×CD3T cell recruitment, Fc-mediated effector functionMalignant ascites, EpCAM-positive gastric and ovarian tumorsMarketed, approved in 2009 by the European Medicines AgencyNeovii Biotech/TriOn PharmaWO2002020039 A3
ErtumaxomabHER2×CD3T cell recruitment, Fc-mediated effector functionHer2-positive breast cancerIIFresenius/TriOn PharmaUS20170210819 A1
FBTA05CD3×CD20T cell recruitmentLymphomaI/IIFresenius/TriOn PharmaWO20080220568 A1
FcΔAdpRegeneron29 December 2010REGN-1979CD3×CD20T cell recruitmentNon-Hodgkin’s lymphoma, B cell lymphoma, acute lymphoblastic leukemia, and chronic lymphocytic leukemiaIRegeneronWO2014047231 A1
Asymmetric reengineering technology-immunoglobulin (ART-Ig)Chugai12 October 2006EmicizumabFIXa×FX2-factor dimerizationHemophilia AMarketed, approved in 2017 by the United States Food and Drug AdministrationRoche, Chugai (Tokyo)WO2006109592 A1
ERY-974CD3×GPC3T cell recruitmentSolid tumorsIChugaiWO2011078332 A1
BiMAbOncoMed24 February 2011OMP-305B83DLL4×VEGF2-ligand inactivationSolid tumorsIOncoMedWO2013044215 A9
BiclonicsMerus24 October 2013MCLA-117CLEC12A×CD3T cell recruitmentAcute myeloid leukemiaIMerusWO2014051433 A1
MCLA-128HER2×HER32-receptor tyrosine kinase inactivationSolid tumorsI/IIMerusWO2015130173 A1
MCLA-158Lgr5×EGFR2-receptor tyrosine kinase inactivationSolid tumorsIMerusWO2016093023 A1
Bispecific Engagement by Antibodies based on the T cell receptor (BEAT)Glenmark27 December 2012GBR-1302HER2×CD3T cell recruitmentHER2 positive cancersIGlenmarkWO2015063339A1
DuoBodyGenmab29 December 2011JNJ-61186372EGFR×cMET2-receptor tyrosine kinase inactivationNon-small-cell lung cancerIJanssen, GenmabWO2014081954 A1
JNJ-63709178CD3×CD123T cell recruitmentAcute myeloid leukemiaIJanssen, GenmabWO2016036937 A1
JNJ-61178104UndisclosedUndisclosedAutoimmune disordersIJanssen, GenmabWO2016052071 A1
AzymetricZymeworks28 June 2012ZW-25Two nonoverlapping epitopes of HER2Receptor tyrosine kinase inactivationHER2-expressing cancersIZymeworksWO2015077891 A1
XmAbXencor10 March 2011XmAb-13676CD3×CD20T cell recruitmentB cell malignanciesINovartis, XencorUS20170174781 A1
XmAb-14045CD3×CD123T cell recruitmentHematological malignanciesINovartis, XencorWO2016086189 A3

(B) Immunoglobulin gamma-like symmetric bispecific antibodies
Dual variable domain-immunoglobulin (DVD-Ig)Abbott18 August 2006ABT-122TNFα×IL-17A2-ligand inactivationPsoriatic arthritis, rheumatoid arthritisIIAbbVie (Abbott)WO2014144280 A3
ABT-165DLL4 × VEGF2-ligand inactivationPhase I in solid tumors/phase II in colorectal cancerI/IIAbbVie (Abbott)WO2014071074 A3
ABT-981IL-1α×IL-1β2-ligand inactivationOsteoarthritisIIAbbVie (Abbott)WO2008082651 A3
SAR156597IL4 + IL132-ligand inactivationIdiopathic pulmonary fibrosisIISanofiUS20170145089 A1
GSK2434735IL4 + IL132-ligand inactivationAsthmaIGlaxoSmithKlineUS20170136581 A1
FynomAbCovagen23 October 2014COVA-322TNFα×IL-17A2-ligand inactivationPlaque psoriasisI/IICovagenWO2011023685 A1
Two-in-one/dual action Fab (DAF)Genentech18 December 2008RG-7597EGFR×HER32-receptor tyrosine kinase inactivationHead and neck, colorectal cancersIIGenentech, RocheWO2010108127 A1

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