Adoptive immunotherapy of murine intracerebral tumors with anti-CD3/interleukin-2-activated tumor-draining lymph node cells.

Abstract

We have recently identified a source of potent antitumor effector cells that can be generated by the sequential culture of tumor-draining lymph node (TDLN) cells with anti-CD3 monoclonal antibody (anti-CD3) and interleukin-2 (IL-2). In this study the therapeutic efficacy of these immune effector cells in the treatment of experimentally induced brain metastases was evaluated. With use of the MCA 205 sarcoma, TDLN cells were harvested from syngeneic B6 mice 9-10 days after subcutaneous inoculation with 10(6) tumor cells. These TDLN cells were activated in vitro by exposure to anti-CD3 for 2 days followed by expansion with IL-2 (10 U/ml) for 3 days. In a neutralization assay, anti-CD3/IL-2-activated cells admixed with MCA 205 tumor cells at an effector/tumor cell ratio of 10 effectively suppressed the growth of tumor cells after intracranial inoculation. In mice with 3-day established brain tumors, multiple intracranial administrations of activated TDLN cells resulted in prolonging survival for which a 50-fold increase in number of cells given intravenously did not. However, the therapeutic effectiveness of systemically (intravenously) administered activated TDLN cells in the treatment of 3-day brain tumors was achieved if tumor-bearing mice were sublethally whole-body irradiated (500 cGy). In two experiments irradiated animals that were not treated or received therapy with IL-2 alone had median survival times (MSTs) of 16 and 17 days, respectively. By contrast, in irradiated animals that received TDLN cells plus IL-2, MST was not reached beyond the observation period of 90 days.(ABSTRACT TRUNCATED AT 250 WORDS)