Donald E. Kern

Specific Adoptive Therapy of Disseminated Tumors

There is little difficulty demonstrating under experimental conditions that T cells can specifically recognize and kill autochthonous or MHC-compatible tumor cells. However, the all too common observation that neoplastic cells can develop and grow progressively in apparently immunocompetent hosts suggests that the cellular immune response is an inadequate defense mechanism for protection from fatal tumors. There are many reasons why the host immune system may be ineffective for controlling tumor growth. The most obvious, and most problematic with regard to immunologic intervention, is that the tumor may not express any determinants immunogenic to the host. Although some tumors may lack such determinants, a substantial amount of evidence is accumulating to suggest that many tumors do express potentially immunogenic surface antigens. The presence of these antigens on tumor cells implies that during progressive growth the tumor may have elicited a quantitatively inadequate response, or may have induced suppressor cells which down-regulated the immune response. Recent technologic and biologic advances have made it possible to purify potential effector T cells and to identify weak antigen-specific T-cell responses by expanding the number of specifically reactive T cells during in vitro culture. Application of these in vitro techniques for analysis of the immune response to tumors has permitted detection of apparent tumor-specific T-cell immunity in cancer patients with a variety of solid tumors and hematologic malignancies.(1–6) Thus, methods to augment such tumor immunity are being explored as potential cancer therapies.