抗 SLAMF7 抗体 Elotuzumab 诱导针对 CLL 细胞系的抗体依赖性细胞介导的细胞毒性作用

SLAMF7, also known as CD319, a SLAM (signaling lymphocytic activation molecule) family receptor, is relatively weakly expressed on chronic lymphocytic leukemia (CLL) B cells.

This study evaluated the ability of elotuzumab (E), an anti-SLAMF7/CD319 antibody, to induce antibody-dependent cellular cytotoxicity (ADCC) against CLL cell lines (MEC-1, MEC-2, CI, HG-3, PGA-1, WA-OSEL). ADCC was assessed by flow cytometry using E (100 μg/mL), rituximab (R, 100 μg/mL), and their combination (E + R). CLL lines served as targets (T), while peripheral blood mononuclear cells (PBMCs) or NK cells from healthy donors served as effectors (E) at an 8:1 E:T ratio for 4 h. With PBMCs, E-induced ADCC ranged from 1. 3 ± 1. 2% (PGA-1) to 14.

6 ± 8. 1% (MEC-1); R-induced ADCC ranged from 9. 2 ± 4. 6% (PGA-1) to 16. 6 ± 9. 4% (WA-OSEL). With NK cells, E-induced ADCC ranged from 1. 8 ± 3. 7% (PGA-1) to 27. 3 ± 4. 7% (MEC-1); R-induced ADCC ranged from 5. 1 ± 4. 3% (PGA-1) to 27. 5 ± 13. 6% (CI). E outperformed R in MEC-1, while R was superior elsewhere. Cell lines with higher SLAMF7/CD319 expression displayed increased sensitivity to E. Cell lines with del17p showed higher SLAMF7/CD319 expression. The combination of E + R showed no significant synergy over monotherapies.

In conclusion, elotuzumab induced significant ADCC in CLL cells, warranting further therapeutic evaluation.