ANTITUMOR IMMUNE-RESPONSE OF HUMAN PERIPHERAL-BLOOD LYMPHOCYTES COENGRAFTED WITH TUMOR INTO SEVERE COMBINED IMMUNODEFICIENT MICE

Here, it is established that human peripheral blood lymphocytes (HuPBL s), injected s.c. with a human lung tumor into severe combined immunod eficient (SCID) mice, engraft and display antitumor cytotoxic activity . Initial studies used HuPBLs from normal donors and an allogeneic tum or cell Line derived from biopsy tissue of a patient with a squamous c ell carcinoma of the lung, Evidence of HuPBL antitumor activity was re vealed by a cell dose-dependent suppression of the tumor xenograft, Tu mor suppression was shown to be dependent upon both CH8+ T cells and C D56+ natural killer cells in the donor HuPBLs. By titrating the antitu mor activity of HuPBLs in SCID mice with and without cytokines, it was established that interleukin (IL)-12 enhanced the HuPBL-mediated tumo r suppression and that IL-2 had a synergistic effect upon the IL-12 en hancement of cytotoxicity, Subsequent studies revealed that a lung can cer patient's PBLs also suppress the growth of the patient's (autologo us) tumor when coinjected s.c. with the tumor cells into SCID mice. Th e patient's antitumor immunity was shown to be mediated by CD8+ T cell s and CD56+ natural killer cells. The data presented here indicate tha t the s.c. coengraftment of HuPBLs and tumor into SCID mice represents a viable model with which to study (and to periodically monitor) pati ents' immune responses to their tumors for extended periods of time an d suggest that this SCID/Winn assay could be used to evaluate novel im munotherapeutic approaches, such as bolus injections of cytokines, cyt okine gene therapy, or vaccination strategies for the treatment of hum an cancer.