An efficient method to prepare T cell receptor gene-transduced cytotoxic T lymphocytes type 1 applicable to tumor gene cell-therapy

Abstract

Genes encoding 2C T cell receptor (TCR) alpha, beta chains from H-2(b)-restricted L(d)-specific CD8(+) cells were successfully transduced into polyclonally activated CD8(+) cells by retroviral modification to generate antigen-specific cytotoxic T lymphocytes (CTL). Antigen-nonspecific CD8(+) T cells polyclonally expanded in the presence of interleukin (IL)-2, Th1 cytokines (interferon (IFN)-gamma and IL-12) and anti-IL-4 monoclonal antibody showed neither cytokine production nor cytotoxicity in response to L(d)-expressing P815 tumor cells. However, 2C-TCR gene-modified CD8(+) T cells exhibited both IFN-gamma production and cytotoxicity in response to P815 tumor cells. The antitumor activity of TCR gene-modified Tc1 cells was also demonstrated in vivo by Winn's assay. Thus, we have developed an efficient method to induce TCR gene-modified antigen-specific Tc1 cells that exhibit antitumor activity both in vitro and in vivo.