A novel approach to generate host antitumor T cells: Adoptive immunotherapy by T cells maturing in xenogeneic thymus

Mouse or human T cells developing in xenogeneic porcine thymus are functional. With efficient peripheral repopulation of mouse T cells by grafting fetal pig thymus (FP THY), B6 nude mice were immunized with inactivated syngeneic melanoma, B16 cells. Splenocytes from B16-immunized FP THY-grafted B6 nude mice efficiently killed B16, but not EL4 target cells in cytotoxicity assays in vitro. Adoptive transfer of splenocytes from B16-immunizd FP THY-grafted B6 nude mice to B16-bearing B6 mice significantly prolonged recipient survival and inhibited B16 solid tumor growth when B16 cells were injected IV or SC, respectively, compared with the identical controls. Splenocytes from nonimmunized FP THY-grafted B6 nude mice failed to protect B6 mice from B16-induced mortality. The present data have demonstrated that mouse T cells maturing in xenogeneic thymus have the ability to kill syngeneic tumor cells. This study may offer a novel resource to produce host antitumor T cells for adoptive immunotherapy of tumor patients.