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

Abstract

Surgical resection of gastric cancer has made significant progress, but majority of patients with advanced gastric cancer face relapse and die within five years. In this study, the antitumor activity of ex vivo expanded T cells against the human gastric cancer was evaluated in vitro and in vivo. Human peripheral blood mononuclear cells were cultured with IL-2-containing medium in anti-CD3 antibody-coated flasks for 5 days, followed by incubation in IL-2-containing medium for 9 days. The resulting populations were mostly CD3+ T cells (97%) and comprised 1% CD3-CD56+, 36% CD3 +CD56+, 11% CD4+, and 80% CD8+. This heterogeneous cell population was also called cytokine-induced killer (CIK) cells. CIK cells strongly produced IFN-γ, moderately TNF-α, but not IL-2 and IL-4. At an effector-target cell ratio of 30:1, CIK cells destroyed 58% of MKN74 human gastric cancer cells, as measured by the 51Cr-release assay. In addition, CIK cells at doses of 3 and 10 million cells per mouse inhibited 58% and 78% of MKN74 tumor growth in nude mouse xenograft assays, respectively. This study suggests that CIK cells may be used as an adoptive immunotherapy for gastric cancer patients.