In recent studies, we demonstrated that the systemic adoptive transfer of
tumor-draining lymph node (LN) cells, activated ex vivo with anti-CD3 mAb or bacterial
superantigens, was effective for treatment of
tumors in the brain, an immunologically privileged site. In this study, we demonstrate that sublethal whole body irradiation (WBI) or local
cranial irradiation of the
tumor-bearing host prior to the adoptive transfer of LN cells, activated with the
superantigen, SEC2, augments therapeutic efficacy, whereas body irradiation with cranial shielding is ineffective. WBI prior to
tumor inoculation or treatment of
tumor-bearing animals with
cyclophosphamide to eliminate suppressor cells did not enhance the therapeutic efficacy of adoptively transferred cells. Analysis of brains by immunohistochemistry, 4 days after cell transfer, revealed a dense infiltrate of SEC2-activated T lymphocytes which exclusively express the
T cell receptor V beta 8.2 phenotype, of both CD4 and CD8 subsets, throughout the
tumors in both irradiated and nonirradiated animals. In addition, MAC-1+ cells were present within
tumors irrespective of either irradiation or cell transfer. These findings demonstrate that the systemically transferred T cells could gain access to the
tumor located in the CNS. However, the therapeutic enhancement by sublethal irradiation does not reflect an increase in T cell or MAC-1+ cell migration into the
tumor.