Adoptive T-Cell Transfer as a Clinical Antitumor Strategy for Hematologic Malignancies

Abstract

Allogeneic stem cell transplantation remains the only widely accepted and effective form of T-cell immunotherapy for blood cancers including lymphoma,myeloma, and leukemia. However this therapy carries substantial risks and is available to only a minority of patients who have suitable donors. The goal of harnessing autologous patient derived) T-cells to treat blood cancers has been elusive. Nonetheless, new insights into T-cell biology and advances in vaccine and T-cell culture technology have provided a foundation for the development and clinical application of autologous T-cell immunotherapy. Two major but intersecting strategies have been used to stimulate antitumor immunity in patients: therapeutic or "active" immunization using putative cancerbased vaccines and "passive" immunization chiefly referring to the transfer of autologous or allogeneic) T-cells into tumor-bearing hosts. This chapter briefly reviews the early studies that formed the basis for adoptive T-cell immunotherapy and then focuses on the growing clinical experience of using adoptive T-cell transfer therapy for immune reconstitution and treatment of hematological malignancies. Historically, most of this experience involves the transfer of cultured, poly-specifi c T-cells obtained from tumor-bearing tissues or peripheral blood. However, advances in the effi ciency and safety of genetransfer technology are driving efforts to generate T-cells with predetermined specifi city for known tumor antigens and enhanced functional properties as well. Recent clinical success using adoptive transfer of genetically altered T-cells in the setting of chronic lymphocytic leukemia and pediatric acute lymphoblastic leukemia, although limited to a small number of patients, has generated increasing interest and has validated the therapeutic potential inherent in T-cell transfer strategies.