Rapid induction of cytolytic T cells via CD28 stimulation for cellular immunotherapy.

Abstract

One approach to adoptive cancer immunotherapy is based on the use of bispecific monoclonal antibodies (mAb) capable to redirect ex vivo generated cytolytic T lymphocytes (CTL) onto tumour cells. The efficiency of the CD28 T-cell activation pathway to induce CD3-dependent cytolytic activity was investigated while avoiding modulation of the TCR/CD3 complex needed for targeting by bispecific mAb. When used e.g. in conjunction with anti-CD2 antibodies or diacylglycerol derivatives, the in vitro stimulation of T cells with anti-CD28 mAb resulted within 36 h in high levels of CD3-dependent cytolysis (tested on a FcR+ target in the presence of anti-CD3 mAb) and sustained lymphokine production, such as TNF alpha, IFN gamma and IL-2, which may affect tumour growth when delivered locally by the transferred T cells. Rapid activation may reduce costly in vitro procedures, preserve homing capacities of retransfused T cells, and thus facilitate implementation of clinical trials based on the use of bispecific antibodies.