Table 1.
TNFR2 antibodies under clinical trials or preclinical developments.
| Name | Producer | Stage of development | Condition or disease | Reported mechanisms | References | |
|---|---|---|---|---|---|---|
| Antagonist | BI-1808 | BioInvent International AB |
Phase 1/2a (NCT04752826): monotherapy or combination with anti-PD-1 (Merck) | Human advanced malignancies | a) Intra-tumor Treg depletion b) CD8+ T-cell expansion c) Modulation of tumor-associated myeloid cells |
(54, 55) |
| BITR2101 | Boston Immune Technologies & Therapeutics Inc. | Preclinical development (IND enabling) | Caner (not detailed) | Not detailed | (56) | |
| APX601 | Apexigen Inc. | Preclinical development (IND enabling) | Mouse cancer model (CT26 and MC38) | a) Blockade of the immunosuppressive functions of both Tregs and MDSCs b) Depletion of TNFR2-expressing Tregs, MDSC, and tumor cells via ADCC and ADCP c) Tumor growth inhibition both as a single agent and in combination with anti-PD-1 |
(57, 58) | |
| AN3025 | Adlai Nortye | Preclinical development | Jurkat cell line Mouse cancer model (MC38) |
a) Treg depletion b) Increased IFNγ and granzyme expression c) Synergistic effect with anti-PD-1 |
(59) | |
| SIM0235 | Simcere | Preclinical development (IND enabling) | Cancer (not detailed) | a) Kill TNFR2+ Tregs and MDSCs through ADCC and ADCP b) Kill TNFR2+ tumor cells c) Synergistic effects with anti-PD-L1 |
(60) | |
| LBL-019 | Nanjing Leads Biolabs Co. Ltd. | Phase 1 (in both China and the USA) | Cancer (not detailed) | Not detailed | (61) | |
| NBL-020 | NovaRock Biotherapeutics | Preclinical development (IND enabling) | Mouse cancer model | a) Enhance CD8 T-cell function through overcoming the suppressive effect from Tregs b) Invigorate exhausted CD8 T cells in an FcγR-dependent manner c) Synergistic effects with anti-PD-L1 |
(62) | |
| Agonist | ||||||
| BI-1910 | BioInvent International AB |
Preclinical development | Mouse cancer model (CT26, MC38 and B16), | a) Increase CD8+ T cell b) Improved CD8/Treg ratios c) synergistic effects with anti-PD-1 |
(63) | |
| HFB200301 | HiFiBiO Therapeutics | Preclinical development (IND enabling) | Mouse cancer model (MC38) | a) Activates CD4+, CD8+ T cells, and NK cells in vitro
b) Expand CD4+T/CD8+T/NK cells in TME without affecting Tregs numbers in vivo |
(64) | |
| MM-401 | Merrimack Pharmaceuticals, Inc. | Preclinical development | T cells from healthy donors; ovarian cancer ascites samples | a) Upregulation of activation markers and cytokine production of CD4+ and CD8+ T cells from Healthy donors b) Promote ADCC and deplete Tregs in ovarian cancer ascites samples |
(65, 66) |
IND, investigational new drug; MDSCs, myeloid-derived suppressor cells; ADCC, antibody-dependent cellular cytotoxicity; ADCP, antibody-dependent cellular phagocytosis.