A syngeneic metastatic tumor model in mice: the natural immune response of the host and its manipulation.

The cell-mediated immune response against a transplantable syngeneic metastatic solid tumor in mice was studied. The immune reactivity of spleen cells from tumor-bearing mice was found to vary during development of the tumor. For about a week after tumor transplantation, the spleen cells were able to protect recipient mice against challenge with tumor cells. Subsequently, the protective activity was replaced by an enhancing activity. Recipient mice that received tumor cells together with spleen cells from mice bearing tumors for about two or three weeks had a higher incidence of tumor takes and larger tumors than controls. This enhancement of tumor development was correlated with the size of the local tumor or metastases in the donors. The enhancing activity was found to be mediated by T lymphocytes and appeared to suppress the protective immune response of the recipients. We devised a system to strengthen the immune response of the host against the development of tumor metastases. In the tumor model used, removal of the local tumor after s.c. transplantation failed to prevent the development of lung metastases and death in most of the mice. However, syngeneic spleen cells which had been sensitized in vitro against tumor cells were found to serve as immunotherapeutic agents. Injection of such spleen cells into mice from which primary tumor implants had been removed surgically led to a markedly increased survival. Spleen cells from both normal and tumor-sensitized donors were effective, but splenocytes from mice bearing large tumors did not reduce metastatic development after sensitization in vitro. Thus, protection against the development of lethal metastases can be achieved with certain types of lymphocytes sensitized in vitro.