Table 3.
Characteristics of antibodies directed to NLSAs.
| Target | mAb (commercial name/originator) | IgG class | MOA | Active indications in HMs (highest phase) | |
|---|---|---|---|---|---|
| Glycoproteins and oncogenic recepteors | CD52 | Alemtuzumab (Campath/University of Cambridge) | Hz IgG1 | ADCC | Approved (CLL) |
| CDC | II (T-PLL/NCT01186640 aC) | ||||
| ADCP? | |||||
| II (PTCL/NCT01806337 aC) | |||||
| CD38 | Daratumumab, JNJ-54767414 (Darzalex/Genmab) | Hz IgG1 | ADCC | Approved (MM) | |
| CDC | II (MCL, DLBCL, FL/NCT02413489 aT) | ||||
| ADCP | |||||
| Blocks CD38 | |||||
| Isatuximab, SAR650984 (ImmunoGen) | Hz IgG1 | ADCC | III (MM/NCT02990338 bR) | ||
| CDC | II (T-ALL, T-NHL/NCT02999633 bR) | ||||
| ADCP | |||||
| Blocks CD38 | |||||
| MOR202, MOR03087 (MorphoSys) | Hz IgG1 | ADCC | I–II (MM/NCT01421186 bR) | ||
| ADCP | |||||
| Blocks CD38 | |||||
| SLAMF7 (CS1, CD319) | Elotuzumab, HuLuc63, BMS-901608 (Empliciti/PDL BioPharma) | Hz IgG1 | ADCC | Approved (MM) | |
| CD37 | BI836826 (Boehringer Ingelheim) | Ch IgG1 | ADCC | II (DLBCL/NCT02624492 bR) | |
| Glyco-Fc | PCD | I (CLL/NCT01296932 aC, NCT02538614 bT) | |||
| Otlertuzumab, TRU-016 (Trubion Pharmaceuticals) | Fv-Fc | ADCC | I–II (CLL/NCT01188681 bC) | ||
| PCD | I (B-NHL/NCT00614042 aC) | ||||
| CD98 (4F2, FRP-1) | IGN523 (Igenica) | Hz IgG1 | ADCC | I (AML/NCT02040506 aC) | |
| CDC | |||||
| PCD | |||||
| DKK-1 | BHQ880 (MorphoSys; Novartis) | Fh IgG1 | Blocks DKK-1 | II (MM/NCT01302886 aC, NCT01337752 aC) | |
| GlycoFc | |||||
| ADCC | |||||
| DKN-01, LY-2812176 (Eli Lilly) | Hz IgG4 | Blocks DKK-1 | I (MM/NCT01711671 bC, NCT01457417 bC) | ||
| CD157 (BST-1) | OBT357, MEN1112 (Menarini; Oxford BioTherapeutics) | Hz IgG1 | ADCC | I (AML/NCT02353143 aR) | |
| GlycoFc | |||||
| GRP78 (BiP) | PAT-SM6 (OncoMab GmbH) | Fh IgM | CDC | I (MM/NCT01727778 aC) | |
| PCD | |||||
| TRAIL-R1 (DR4) | Mapatumumab, TRM1, HGS-1012 (Cambridge Antibody Technology) | Fh IgG1 | PCD | I (NHL, HL/NCT00094848 aC) disc. | |
| II (MM/NCT00315757 bC) disc. | |||||
| ROR-1 | Cirmtuzumab, UC-961 (University of California, San Diego) | Hz IgG1 | PCD | I–II (CLL, MCL/NCT03088878 bNYR) | |
| Blocks ROR-1 | |||||
| I (CLL/NCT02860676 aE, NCT02222688 aR) | |||||
| Notch-1 | Brontictuzumab, OMP-52M51 (OncoMed Pharmaceuticals) | Hz IgG2 | Blocks Notch-1 | I (HM/NCT01703572 aC) disc. | |
| TfR1 (CD71) | E2.3/A27.15 (University of Arizona) | mIgG1 | Blocks TfR1 | I (HM/NCT00003082 aC) | |
| EPHA3 | Ifabotuzumab, KB004 (Ludwig Institute for Cancer Research) | Hz IgG1 | ADCC | I–II (AML/NCT01211691 aS) | |
| PCD | |||||
| HLA-DR | IMMU114, hL243 (Immunomedics) | Hz IgG4 | PCD | I (B-NHL/NCT01728207 aR) | |
| G(M2) | BIW-8962 (Kyowa Hakko Kirin Co.) | Hz IgG1 | ADCC | I (MM/NCT00775502 aT) | |
| Chemokine receptors | CCR4 | Mogamulizumab, KW-0761 (Poteligeo/Kyowa Hakko Kirin Co.) | Hz IgG1 | ADCC | Approved (ATL, CTCL, PTCL) |
| II (NK-lymphoma/NCT01192984 aC) | |||||
| CXCR4 | Ulocuplumab, BMS-936564, MDX-1338 (Medarex) | Hz IgG4 | Blocks CXCR4 | I–II (AML/NCT02305563 bR) | |
| I (MM/NCT01359657 bC) | |||||
| I (CLL, DLBCL, FL/NCT01120457 aC) | |||||
| PF-06747143 (Pfizer) | Hz IgG1 | ADCC | I (AML/NCT02954653 bR) | ||
| CDC | |||||
| Blocks CXCR4 | |||||
| Soluble factors and associated receptors | BAFF | Tabalumab, LY2127399 (Eli Lilly) | Fh IgG4 | Blocks BAFF | II (MM/NCT01602224 bC) disc. |
| BAFF-R | VAY736 (MorphoSys; Novartis) | Fh IgG1 | Blocks BAFF-R | I (CLL/NCT02137889 aT) | |
| ADCC | |||||
| GlycoFc | |||||
| RANKL | Denosumab, AMG-162 (Prolia; Ranmark; Xgeva/Amgen) | Fh IgG2 | Blocks RANKL | III (MM/NCT01345019 aANR) | |
| II (MM/NCT00259740 aC, NCT02833610 aR) | |||||
| II (NHL with hypercalcemia/NCT00896454 aC) | |||||
| IL-6 | Siltuximab, CNTO-328 (Sylvant/Centocor) | Ch IgG1 | Blocks IL-6 | II (MM/NCT00911859 bC, NCT00402181 aC) | |
| IL-6R | Tocilizumab, R-1569 (Actemra/Chugai Pharmaceutical; Osaka University) | Hz IgG1 | Blocks IL-6R | I (CLL/NCT02336048 bR) | |
| I (MM/NCT02447055 bW) disc. | |||||
| IL-3Rα (CD123) | CSL360 (CSL) | Ch IgG1 | ADCC | I (AML/NCT00401739 aC) | |
| CDC | |||||
| Blocks IL-3Rα | |||||
| Talacotuzumab, JNJ-56022473, CSL362 (CSL) | Hz IgG1 GlycoFc | ADCC | III (AML/NCT02472145 bANR) | ||
| Blocks IL-3Rα | |||||
| II (MDS/NCT03011034 bR) | |||||
| XmAb14045 (Xencor) | Fh IgG1 | ADCC | I (AML, B-ALL, DC Neoplasm, CML/NCT02730312 aR) | ||
| KHK2823 (Kyowa Hakko Kirin Co.) | Fh IgG1 | ADCC | I (AML, MDS/NCT02181699 aANR) | ||
| IL-2Rα (CD25) | Basiliximab, SDZ-CHI-621 (Simulect/Novartis) | Ch IgG1 | Blocks IL-2Rα | II (AML, CML, ALL, CLL, HL, MM/NCT00975975 aC) | |
| Daclizumab | Hz IgG1 | Blocks IL-2Rα | II (ATL/NCT00001941 aC) | ||
| II (MM, NHL/NCT00006350 bC) | |||||
| IGF-1R (CD221) | Ganitumab, AMG-479 (Amgen) | Fh IgG1 | Blocks IGF-1R | I (NHL/NCT00562380 aC) | |
| Figitumumab, CP-751871 (Pfizer) | Fh IgG2 | Blocks IGF-1R | I (MM/NCT01536145 aC) disc. | ||
| Dalotuzumab, MK-0646 (Pierre Fabre) | Hz IgG1 | Blocks IGF-1R | I (MM/NCT00701103 aC) disc. | ||
| AVE1642 (ImmunoGen) | Hz IgG1 | Blocks IGF-1R | I (MM/NCT01233895 aC) disc. | ||
| GM-CSF (CSF2) | Lenzilumab, KB003 (KaloBios Pharmaceuticals) | Hz IgG1 | Blocks GM-CSF | I–II (CMML/NCT02546284 aR) | |
| HGF | Ficlatuzumab, AV-299 (AVEO Pharmaceuticals) | Hz IgG1 | Blocks HGF | I (NHL, HL, MM/NCT00725634 bC) | |
| I (AML/NCT02109627 bR) | |||||
| Adhesion molecules | CD44 | RG7356, RO5429083 (Chugai Biopharmaceuticals; Roche) | Hz IgG1 | Blocks CD44 | I (AML/NCT01641250 bC) |
| VLA-4 (CD49d) | Natalizumab, BG-0002-E (Tysabri/Elan Corporation) | Hz IgG4 | Blocks VLA-4 | I–II (MM/NCT00675428 aT) disc. | |
| ICAM-1 (CD54) | BI-505 (BioInvent International) | Fh IgG1 | ADCC | I (MM/NCT01025206 aC) | |
| ADCP | II (sMM/NCT01838369 aC) | ||||
| PCD | |||||
| Angiogenesis | VEGF-A | Bevacizumab (Avastin/Genentech; Hackensack University Medical Center) | Hz IgG1 | Blocks VEGF-A | II (MM/NCT00482495 aC, NCT00473590 bC) |
| II (CLL/NCT00290810 aC, NCT00448019 bC) disc. | |||||
| III (DLBCL/NCT00486759 bT) disc. | |||||
| II (FL/NCT00193492 bC) | |||||
| Endosialin (CD248, TEM1) | Ontecizumab, MORAB-004 (Ludwig Institute for Cancer Research; Morphotek) | Hz IgG1 | Blocks endosialin | I (HM/NCT01748721 aC) | |
Antibodies that reached clinical studies. Biosimilars and immunoconjugates are excluded.
aMonotherapy.
bCombined therapy.
mAb, monoclonal antibody; MOA, mechanisms of action; HMs, hematological malignancies; Ch, human–mouse chimeric; Fh, fully human; Hz, humanized; m, mouse; Glyco-Fc, glycoengineered Fc fragment; CDC, complement-dependent cytotoxicity; ADCC, antibody-dependent cell-mediated cytotoxicity; ADCP, antibody-dependent cell-mediated phagocytosis; PCD, programmed cell death; B-NHL, B-cell non-Hodgkin’s lymphoma; HL, Hodgkin’s lymphoma; CLL, chronic lymphocytic leukemia; FL, follicular lymphoma; DLBCL, diffuse large B-cell lymphoma; MCL, mantle cell lymphoma; MM, multiple myeloma; B-ALL, B-cell acute lymphoblastic leukemia; T-PLL, T-cell prolymphocytic leukemia; PTCL, peripheral T-cell lymphoma; CTCL, cutaneous T-cell lymphoma; ATL, adult T-cell leukemia and lymphoma; AML, acute myeloid leukemia; CML, chronic myeloid leukemia; CMML, chronic myelomonocytic leukemia; MDS, myelodysplastic syndrome; DC, dendritic cells; disc., discontinued in hematological malignancies; NCT, number of clinical trial (clinicaltrials.gov); C, completed; R, recruiting; T, terminated; ANR, active non-recruiting; NYR, not yet recruiting; E, enrolling by invitation; T, terminated; S, suspended; W, withdrawn.