Kamonporn Kotemul, Ratthakorn Chaiwut, Chaochetdhapada Putpim, Supansa Pata, Witida Laopajon, Chatchai Tayapiwatana, Watchara Kasinrerk, Nuchjira Takheaw
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.
