Human cytotoxic lymphocytes reactive with pancreatic adenocarcinoma cells

In this study we describe the establishment of long-term cytotoxic T lymphocyte (CTL) cell lines and clones from lymph nodes of 9 pancreatic cancer patients by stimulation with allogeneic pancreatic tumor cell lines. The CTL cells exhibited strong cytolytic activity against many, but not all, allogeneic pancreatic tumor cell lines, but showed little or no reactivity against most nonpancreatic tumor cells, indicating they were detecting non-HLA antigens. Most of the cells from the established CTL cell lines were CD3+, and the CD8 antigen was also expressed on the majority of the cells. Occasional cultures exhibited a broad spectrum of cytolytic activity, and such CTL cell lines showed high expression of the natural killer (NK) cell markers, Leu-19 and Leu-11b. Seven clones were established from two CTL cell lines (LT and RE). These clones exhibited functional and phenotypic heterogeneity. The cytolytic activity of CTL cell lines and clones was inhibited by antibodies to CD3 antigen. Immunoprecipitation experiments using an anti-CD3 monoclonal antibody (Leu4) or anti-alpha/beta T cell receptor antibody (beta f1) revealed the presence of two bands of Mr 40,000 and Mr 50,000 in clones positive for the alpha/beta T cell receptor. The in vivo effects of the LT cytotoxic clones were studied in the Winn assay using pancreatic tumor xenografts in nude mice. Subcutaneous injections of a mixture of the cytotoxic clones and pancreatic tumor cells resulted in a complete inhibition of tumor development, whereas mice given injections of tumor cells and CTL clones that lacked cytotoxic activity against pancreatic cells developed tumors.