Antitumor Immune Response of Human Peripheral Blood Lymphocytes Coengrafted with Tumor into Severe Combined Immunodeficient Mice

Abstract

Here, it is established that human peripheral blood lymphocytes (HuPBLs), injected s.c. with a human lung tumor into severe combined immunodeficient (SCID) mice, engraft and display antitumor cytotoxic activity. Initial studies used HuPBLs from normal donors and an allogeneic tumor cell line derived from biopsy tissue of a patient with a squamous cell carcinoma of the lung. Evidence of HuPBL antitumor activity was revealed by a cell dose-dependent suppression of the tumor xenograft. Tumor suppression was shown to be dependent upon both CD8+ T cells and CD56+ natural killer cells in the donor HuPBLs. By titrating the antitumor activity of HuPBLs in SCID mice with and without cytokines, it was established that interleukin (IL)-12 enhanced the HuPBL-mediated tumor suppression and that IL-2 had a synergistic effect upon the IL-12 enhancement of cytotoxicity. Subsequent studies revealed that a lung cancer patient's PBLs also suppress the growth of the patient's (autologous) tumor when coinjected s.c. with the tumor cells into SCID mice. The patient's antitumor immunity was shown to be mediated by CD8+ T cells and CD56+ natural killer cells. The data presented here indicate that the s.c. coengraftment of HuPBLs and tumor into SCID mice represents a viable model with which to study (and to periodically monitor) patients' immune responses to their tumors for extended periods of time and suggest that this SCID/Winn assay could be used to evaluate novel immunotherapeutic approaches, such as bolus injections of cytokines, cytokine gene therapy, or vaccination strategies for the treatment of human cancer.