Induction of T Lymphocytes Specific to Human Gastric Cancer Using HLA-A Matched Allogeneic Gastric Tumor Cells

Abstract

Tumor-specific cytotoxic T lymphocytes (CTLs) from patients with early-stage tumors are usually more efficient at attacking tumor cells than CTLs from the progressing tumor stages. The authors investigated the antitumor activity of CTLs from gastric cancer patents and healthy donors. In this study, peripheral blood lymphocytes (PBLs) from gastric cancer patients and healthy donors were stimulated with HLA-A matched allogeneic gastric cancer cells such as KATO-3, MKN45, and SGC7901. Three different populations of lymphocyte, p5-CTL-KATO, h4-CTL-MKN45, and h4-CTL-KATO, were induced and expanded. Flow cytometry analyses showed that 85.2% to 97.8% of these cells were CD3-positive and 45.5% to 51.2% were CD8-positive. The induced CTLs efficiently kill HLA-A2 or HLA-A24 gastric cancer cells through CTL-mediated cytotoxicity. However, no effects were observed for other cancer cells or HLA-A2 negative gastric cancer cells. The specific cytotoxicity of the induced CTLs was further confirmed by cold-target inhibition and monoclonal antibody blockage. These results suggest that CTL-mediated cytotoxicity specific for tumor cells can be produced by stimulating PBLs from healthy donors using HLA-A matched tumor cells, which will lead to the development of new immunotherapeutic strategies to kill cancer cells.

Adoptive immunotherapy of human gastric cancer with ex vivo expanded T cells

“…One tumor-specific antigen, MG7-antigen, shows great potential for predicting early cancer as well as for inducing immune responses to gastric cancer (Guo et al, 2002;Wu et al, 2009). Using HLA-A-matched allogeneic gastric cancer cells to induce tumor-specific CTLs appears to be an alternative immunotherapy option for gastric cancer (Nie et al, 2003). Dendritic cell-based vaccination strategies have yielded promising results in experimental tumor models and in clinical studies (Brossart et al, 2000;Kalergis and Ravetch, 2002).…”

Immunotherapeutic Strategies for Gastric Carcinoma: A Review of Preclinical and Clinical Recent Development

“…Nie et al used different HLA-A matched allogeneic GC cells to stimulate peripheral blood lymphocytes from GC patients or from healthy donors and assessed them against different cell lines. Induced CTLs had antitumor effects against HLA-A2 and HLA-A24 GC cell lines with no effect against HLA-A2 negative GC cells or any other cancer cells [30]. When TILs and specific T-cells from peripheral blood of GC patients are expanded in vitro, they show specific type 1 T-cells response to GC antigens.…”

Novel Immunotherapeutic Strategies of Gastric Cancer Treatment

“…One tumor-specific antigen, MG7-antigen, shows great potential for predicting early cancer as well as for inducing immune responses to gastric cancer [93, 94]. Using HLA-A-matched allogeneic GC cells to induce tumor-specific CTLs appears to be an alternative immunotherapy option for gastric cancer [95]. …”