Induction of cytotoxic T lymphocytes from peripheral blood of human histocompatibility antigen (HLA)-A31(+) gastric cancer patients by in vitro stimulation with antigenic peptide of signet ring cell carcinoma

Antigenic peptides have been used as a cancer vaccine in melanoma patients and have led to a drastic regression of metastatic tumors. However, few ant igens have been identified in non-melanoma tumors. We recently purified a n ew natural antigenic peptide, designated F4.2, by biochemical elution from a human gastric signer cell carcinoma cell line and showed that it is recog nized by an autologous human histocompatibility antigen (HLA)-A31-restricte d cytotoxic T lymphocyte (CTL) clone. Here we describe in vitro induction o f F4.2-specific CTLs from peripheral blood T lymphocytes of HLA-A31(+) gast ric cancer patients. The T cells of seven HLA-A31(+) patients with gastric cancers were stimulated in vitro by F4.2-pulsed autologous dendritic cells which had been induced from peripheral blood of each patient by incubation in the presence of granulocyte macrophage colony-stimulating factor (GM-CSF ) and IL-4. We tested the cytotoxicity of the T cells against F4.1-londed C 1R-A*31012 by a 6-h Cr-51 release assay after 3 stimulations with F4.2-puls ed dendritic cells, F4.2-specific cytotoxicity was detectable in the stimul ated T cells from two of the seven HLA-A31(+) patients, Further, both F4.2- specific CTLs also lysed the gastric cancer cell line, HST-2. from which F4 .2 mas derived. These results suggest that F4.2 peptide may be useful as an HLA-A31-restricted peptide vaccine in certain patients with gastric cancer .