Induction of alloreactive cytotoxic T lymphocytes by intra-splenic immunization with allogeneic class I major histocompatibility complex DNA and DC-chol cationic liposomes

Abstract

A simple strategy for designing a cancer immunotherapeutic system involves modification of tumor cells from tumor-bearing animals in vivo in such a way that the host can evoke a specific immune response against them. We have expressed allogeneic class I major histocompatibility complex (MHC) molecules on tumor cells, through ex vivo DNA-mediated gene transfer. These molecules are potent immuno-modulators for the stimulation of strong immune reactions against certain malignancies. In order to achieve efficient gene delivery to tumor cells in vivo, we have compared the efficiencies of gene transfer into mammalian tumor cells by the biolistic particle delivery system and cationic liposomes. In this report, we have demonstrated that cationic liposomes prepared by DC-chol and DOPE gives the best efficiency of transfection for tumor cells in vivo. We also showed that a strong anti-H-2Kb allo-reactive cytotoxic T lymphocyte (CTL) response could be generated following in vivo immunization of AKR/J mouse spleens with the H-2Kb gene and DC-chol cationic liposomes. The direct immunization of mouse spleens to induce cell-mediated immunity against exogenous antigens may allow alternative treatment strategies for cancer immunotherapy.