Rationale for a novel immunotherapy of cancer with allogeneic lymphocyte infusion

A simple method of cancer immunotherapy has been developed which achieves marked objective response in 20-30% of patients with disseminated disease. Each course consists of a low dose of chemotherapy followed two days later by intravenous infusion of allogeneic lymphocytes. Courses are repeated on a monthly basis as needed. The function of the chemotherapy--too mild to significantly influence tumor growth directly--appears to be depletion of suppressor T cells, which sensitizes the patient to the immunostimulant action ("allogeneic effect") of the subsequently infused lymphocytes. The rationale for this method is discussed in the context of a review of past attempts at lymphocyte immunotherapy. We are now attempting to improve response rates by combatting anergy with nutritional immunopotentiators, and by preventing prostaglandin-mediated or -dependent immunosuppression with prostaglandin synthetase inhibition. By understanding and counteracting the various specific and general means by which a growing tumor induces host tolerance, it should prove possible to achieve immune-mediated tumor regression in a high proportion of patients. Best results may be seen when allogeneic lymphocyte therapy is initiated at an earlier stage of the disease, and is used in conjunction with surgery, radiotherapy, short-course intensive chemotherapy, or hyperthermia-based methods.