# The Anti-SLAMF7 Antibody, Elotuzumab, Induces Antibody-Dependent Cellular Cytotoxicity Against CLL Cell Lines

## TL;DR

Elotuzumab, an antibody targeting SLAMF7, can kill chronic lymphocytic leukemia cells through a process called antibody-dependent cellular cytotoxicity.

## Contribution

This study demonstrates elotuzumab's ability to induce ADCC in CLL cell lines, highlighting its potential as a therapeutic option.

## Key findings

- Elotuzumab induced ADCC in CLL cell lines, with varying effectiveness depending on the cell line and effector cells used.
- Higher SLAMF7/CD319 expression in cell lines correlated with increased sensitivity to elotuzumab.
- Combining elotuzumab with rituximab did not significantly enhance cytotoxicity compared to monotherapies.

## Abstract

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.