Differential control of human Treg and effector T cells in tumor immunity by Fc-engineered anti–CTLA-4 antibody
Year: 2018
Type: article
Abstract: 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.
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Study of the function and development of regulatory T cells, G3683196383, Association of immune responses with racial differences of cancer development, G4577801730, Loss of melanocyte nitche and its regeneration in vitiligo, G8883393197, The role of the transcription factor Tox2 in Treg and Tfh biology
OpenAlex ID: W2907885272