Antigen-specific cultured T cells can mediate tumor therapy and provide long-term immunologic memory in vivo

Abstract

One goal of our research has been to define the principles necessary to utilize cultured T cells as reagents in vivo in order to augment specific T cell immunity and to utilize the augmented immunity as a form of cancer therapy. A potential barrier for the use of cultured T cells in vivo has been the previously demonstrated inability of cultured T cells to survive in vivo. As an example, studies to be reviewed below showed that a small precursor population of tumor-specific T cells could be grown to large numbers in vitro by repeated supplementation of media with exogenous Interleukin 2 (IL 2) and that the resultant long-term cultured T cells could mediate specific tumor therapy in vivo. However, T cells grown with IL 2 lost the ability to proliferate in response to immune stimulation by tumor antigen, became dependent upon exogenous IL 2 for survival, and thus died rapidly in vivo without repeated administration of exogenous IL 2. By contrast, T cells grown long-term in vitro in response to antigen-stimulation, as opposed to exogenous IL 2, were able to proliferate in vivo in response to stimulation by tumor antigen, mediate tumor therapy and persist long-term in vivo as functional memory T cells. Thus, the previously demonstrated inability of cultured T cells to survive and persist in vivo apparently resulted from the culture conditions utilized and did not reflect an intrinsic defect of all cultured T cells.