Immunotherapy of cancer by systemic administration of lymphoid cells plus interleukin-2.

The adoptive transfer of specifically immune lymphocytes is capable of mediating the regression of a variety of established experimental tumors. We have studied the factors responsible for successful adoptive immunotherapy. Following injection of FBL-3 lymphoma into the footpad of syngeneic mice, this tumor forms a local nodule and is disseminated throughout the mouse within 5 days. Systemic administration of fresh immune lymphocytes on day 5, or of in vitro boosted immune splenocytes, or immune lymphoid cells expanded in interleukin-2 (IL-2), is capable of mediating total regression of both local and disseminated tumor. The efficacy of this immunotherapy can be enhanced by the simultaneous administration of IL-2. Because specifically immune cells can be difficult to obtain in many murine and human tumor systems, we have investigated the use of nonspecifically sensitized cells for use in adoptive immunotherapy. Lymphokine-activated killer cells (LAK) can easily be generated by incubating fresh murine or human lymphocytes in IL-2. Systemic injection of LAK cells can reduce the growth of established pulmonary metastases in murine tumor models when the LAK cells are administered in conjunction with IL-2. A variety of methods for activating human lymphoid cells to become lytic for fresh human tumors have been developed, including activation by IL-2, activation by lectins such as phytohemagglutinin and concanavalin A, and by allosensitization with pooled stimulator cells. The characteristics of these different activated killer cells have been defined. In a series of Phase I studies, we have demonstrated that activated killer cells can be safely administered to humans with advanced cancer. Studies are actively proceeding to develop an effective and practical method for the adoptive immunotherapy of cancer in humans, using both specifically activated and nonspecifically activated lymphoid cells.