Bispecific Antibody‐directed Antitumor Activity of Human CD4(+) Helper/Killer T Cells Induced by Anti–CD3 Monoclonal Antibody plus Interleukin 2

Freshly isolated human CD4(+) T cells can not respond to recombinant interlenkin 2 (rIL–2) because of their lack of p75 IL–2 receptor expression. However, we succeeded In inducing a marked proliferation of purified CD4(+) T cells by activation with rIL–2 plus anti–CD3 monoclonal antibody (mAb) cross–linked to a plastic plate. The proliferated CD4(+) T cells produced a significant amount of IL–2 upon stimulation with phorbol ester plus A23187. Interestingly, CD4(+) T cells activated with anti–CD3 mAb plus rIL–2 revealed a strong cytotoxic activity against Fc receptor (FcR)–positive tumor cells in the presence of anti–CD3 mAb. Moreover, the CD4(+) T cells could lyse FcR–negative glioma cells by targeting with bispecific mAb containing anti–CD3 mAb and anti–glioma mAb. Thus, we demonstrated that rIL–2 and immobilized anti–CD3 mAb allowed the rapid generation of human CD4(+) helper/killer T cells, which may be useful for the development of a new adoptive tumor immunotherapy.