Induction of Cytotoxic T Lymphocytes from Peripheral Blood of Human Histocompatibility Antigen (HLA)-A31+Gastric Cancer Patients byin vitroStimulation with Antigenic Peptide of Signet Ring Cell Carcinoma

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Abstract
Antigenic peptides have been used as a cancer vaccine in melanoma patients and have led to a drastic regression of metastatic tumors. However, few antigens have been identified in non‐melanoma tumors. We recently purified a new natural antigenic peptide, designated F4.2, by biochemical elution from a human gastric signet cell carcinoma cell line and showed that it is recognized by an autologous human histocompatibility antigen (HLA)‐A31‐restricted cytotoxic T lymphocyte (CTL) clone. Here we describe in vitro induction of F4.2‐specific CTLs from peripheral blood T lymphocytes of HLA‐A31+ gastric 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 F4.2‐loaded C1R‐A *31012 by a 6‐h 51Cr release assay after 3 stimulations with F4.2‐pulsed dendritic cells. F4.2‐specific cytotoxicity was detectable in the stimulated 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 was derived. These results suggest that F4.2 peptide may be useful as an HLA‐A31‐restricted peptide vaccine in certain patients with gastric cancer.

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