Differential control of human Treg and effector T cells in tumor immunity by Fc-engineered anti–CTLA-4 antibody

著者: Danbee Ha, Atsushi Tanaka, Tatsuya Kibayashi, Atsushi Tanemura, Daisuke Sugiyama, James B. Wing, Ee Lyn Lim, Karen Wei Weng Teng, Dennis O. Adeegbe, Evan W. Newell, Ichiro Katayama, Hiroyoshi Nishikawa, Shimon Sakaguchi - Proceedings of the National Academy of Sciences, PNAS 2018 被引用: 200

Significance Anti–CTLA-4 mAb is able to augment tumor immunity despite CTLA-4 expression by functionally opposing T cell populations: activated effector T (Teff) cells and FOXP3 + CD4 + Treg cells. Here we show that anti–CTLA-4 mAb engineered to be cytotoxic depleted Treg cells effectively in vitro in humans and in vivo in mice. It expanded antigen-specific CD8 + Teff cells when tumor-antigen stimulation was delayed several days to protect them from killing by the mAb. Anti–CTLA-4 mAb modified to exhibit a lesser or no cell-depleting activity failed to show such effects. This strategy of differentially controlling Treg and Teff cells by cytotoxic anti–CTLA-4 mAb to evoke effective tumor immunity will help in designing cancer immunotherapy targeting other molecules commonly expressed by Treg and Teff cells.