Evaluating the immune effector functions induced by humanized anti-CD99 antibody in eliminating T lymphoblastic leukemia/lymphoma cells

Abstract

Monoclonal antibodies (mAbs) have emerged as targeted immunotherapies with clinical effectiveness and low adverse effects for various cancers. However, antibody drugs for treating aggressive T cell malignancies, T lymphoblastic leukemia/lymphoma (T-ALL/T-LBL), are still limited. Therefore, a potential mAb for treating T-ALL/T-LBL with minimal toxicity to normal cells needs to be developed. We have previously demonstrated that our in-house produced mouse anti-human CD99 mAb MT99/3 and its humanized version, HuMT99/3, which recognize a newly identified epitope of CD99 can induce apoptosis of T-ALL/T-LBL cells without affecting non-malignant peripheral blood cells. Nevertheless, the immune effector functions activated by HuMT99/3 against T-ALL/T-LBL cells remain unexplored. In this study, we evaluated the anticancer activities of HuMT99/3 against T-ALL/T-LBL cells via immune effector functions. T-ALL/T-LBL cell lines were used as target cells, including Jurkat E6.1, MOLT-4, and SUP-T1. The results demonstrated that HuMT99/3 could mediate potent antibody-dependent cellular cytotoxicity (ADCC) activity to kill all cell lines by activating the Fc receptor CD16 on effector cells. HuMT99/3 significantly enhanced the phagocytosis of monocytes on all three malignant T cell lines through antibody-dependent cellular phagocytosis (ADCP) activity. In addition, HuMT99/3 could activate complement to destroy T-ALL cell lines through complement-dependent cytotoxicity (CDC) activity, without affecting the T-LBL cell line and normal PBMCs. Furthermore, the mAb MT99/3 significantly inhibited tumor growth in a T-ALL xenograft model. These findings provide valuable insights into the development of monoclonal antibodies targeting CD99 as promising therapeutics for T-ALL/T-LBL treatment with minimal toxicity to normal peripheral blood cells. © The Author(s) 2025.