Induction of tumor-specific in vivo protective immunity by immunization with tumor antigen-pulsed antigen-presenting cells.

The present study investigates the role of antigen-presenting cells (APC) in inducing tumor-specific in vivo protective immunity. Thy-1+ cell-depleted, Mac-1+ cell-enriched fraction of normal BALB/c spleen cells were used as a source of APC. These APC were cultured in vitro with the membrane fraction isolated from Rous sarcoma virus-induced CSA1M fibrosarcoma derived from BALB/c strain. The administration of such APC into naive BALB/c mice generated the capacity of these animals to reject the subsequently challenged viable CSA1M tumor cells. The induction of anti-CSA1M in vivo protective immunity required three consecutive immunizations with more than 10(5) APC which had been pulsed in vitro with 200 micrograms protein component of CSA1M membrane fraction. This immunity was tumor-specific, since the inoculation of CSA1M or Meth A fibrosarcoma membrane component-pulsed APC resulted in the selective immunity against the challenge with homologous types of tumor cells. The CSA1M-specific in vivo protective immunity was also induced by injecting APC pulsed with solubilized CSA1M membrane components. Moreover, it was demonstrated that the efficiency for inducing anti-CSA1M immunity was much higher in the utilization of tumor antigen-pulsed APC than in the immunization with tumor antigens emulsified in complete Freund's adjuvant. These results indicate the crucial role of APC in generating tumor rejection immunity in vivo, and this model presents a novel approach to induce tumor-specific immunity without utilizing tumor cells themselves.