Table 2.
Preclinical bispecific and trispecific antibodies in multiple myeloma
| Target | Drug | Sponsor | Notes |
|---|---|---|---|
| BCMAxCD3 | EM801 | Bristol Myers Squibb | Active also in high-risk patients and non–cross-resistant with previous lines of treatment (14) |
| BCMAxCD3 | AP163 | Ampsource Biopharma Shanghai Inc. | Induces less cytokine secretion than other bispecifics in vitro (16) |
| BCMAxNKp30 | CTX-8573 | Compass Therapeutics | Antitumor effect in mice even with low BCMA expression (9) |
| BCMAxCD16a | AFM26 | Affimed Therapeutics | NK-cell engager; may have superior safety profile over CD3 T-cell engagers (15) |
| BCMAxCD16a | RO7297089 | Genentech | Has a favorable safety profile and represents a novel MOA among other BCMA-targeting modalities (10) |
| BCMAxMICA | 2A9-MICA | China Pharmaceutical University | MICA binds NKG2D on NK cells to induce multiple myeloma cell death in vitro and in a mouse model (24) |
| BCMAxCD200xCD16a | Gantke et al. | Affimed Therapeutics | Results in increase in avidity leading to preferential lysis of antigen double-positive cells compared with antigen single-positive cells (7) |
| CD138xCD3 | STL001 | Jiangsu, China | Nanomolar-level affinity to recombinant human CD138 protein and shows more potent antitumor activity against RPMI-8226 cells than that of separate aCD3-ScFv-hIgFc and aCD138-ScFv-hIgFc, or the isotype mAb in vitro or in vivo (17) |
| CD138xCD3 | h-STL002, m-STL002 | Jiangsu, China | Shows potent cytotoxicity against multiple myeloma RPMI-8226 cell line through T-cell activation (18) |
| CD38xCD3xCD28 | Wu et al. | Sanofi | Demonstrates in vitro multiple myeloma cell killing 3–4 log higher than daratumumab (12) |
| CD38xCD3 | Sorrento CD38/CD3 | Sorrento Therapeutics | Demonstrates more potent tumor cell killing than daratumumab (19) |
| CD38xCD3 | Bi 38–3 | Inserm | Kills multiple myeloma cells in vitro and in a mouse model with no toxicity to B, T, and NK cells (23) |
| SLAMF7xNKG2D | SLAMF7-NKG2D | Ohio State University | In vivo, survival was significantly prolonged using SLAMF7-NKG2D biAb in a xenograft NOD-SCIDIL2γc−/− (NSG) mouse model engrafted with both human PBMCs and multiple myeloma cell lines (22) |
| GPRC5DxCD3 | GPRC5DxCD3 TRAB | Chugai Pharmaceutical | Suppresses tumor growth of GPRC5D-positive myeloma cells through the activation of T cellsin vitro and in vivo in xenograft models (20) |
| NY-ESO-1xCD3 | ImmTAC-NYE | Immunocore | Produces lysis of multiple myeloma cell line in vitro (25) |
| A2/NY-ESO-1xCD3 | Maruta et al. | Ehime University, Japan | Antimyeloma activity in vitro similar to CAR-T construct (26) |
Abbreviations: biAb, bispecific antibody; mAb, monoclonal antibody; MOA, mechanism of action; PBMC, peripheral blood mononuclear cell.