Generation of Human Cytotoxic T Lymphocytes Against Autologous Solid Tumors by Autologous Mixed Lymphocyte Tumor Cell Culture with T Cell Growth Factor

Abstract

Autologous mixed lymphocyte tumor cell cultures (MLTC) generated cytotoxicity against autologous tumors in 5 out of 15 (33%) patients with head and neck cancer. Further cultivation of MLTC-activated lymphocytes with T cell growth factor (TCGF) resulted not only in the propagation of cytotoxic T lymphocytes (CTL) and an increase of cytotoxicity against autologous tumors, but also in the induction of killer cells against allogeneic tumor cells. The results of crisscross tests using fresh tumor cells from 17 donors and lymphocytes from 10 donors indicate that cultivation of MLTC-activated lymphocytes with TCGF generated killer cells cytotoxic for allogeneic tumors in most cases, but not for autologous or allogeneic phytohemagglutinin-induced lymphoblasts. Further, the results of a cold target inhibition test undertaken in an autologous tumor killing system suggest that at least 2 different subsets, specifically cytotoxic for autologous tumors and cytotoxic for both autologous and allogeneic tumors, were developed in the CTL induced by autologous MLTC followed by cultivation with TCGF. The phenotypes of the effector cells were shown to be OKT3+, Leu2a+, OKT8+, OKM1-, and Leu7- by blocking assay using complement and monoclonal antibody against the T cell surface marker.