Cancer Vaccines and T Cell Therapy

Abstract

The treatment of hematological malignancies by harnessing immune responses has long been pursued. It is well accepted that the success of allogeneic hematopoietic stem cell transplantation (HSCT) as a treatment for hematological malignancies is due primarily to immunologic recognition and elimination of recipient leukemia cells by donor T cells, the so-called graft versus leukemia (GVL) effect. Based on the discovery and identification of leukemia antigens, it is now possible to target leukemia either by specific vaccination or adoptive transfer of in vitro generated anti-leukemia cytotoxic lymphocytes (CTLs). Leukemia antigens can be categorized broadly into 3 classes: (1) ubiquitously expressed alloantigens, also known as minor histocompatibility antigens (mHags), widely expressed by normal tissues in the recipient as well as by leukemia cells, and capable of initiating both GVHD and GVL responses; (2) alloantigens expressed uniquely by cells of the hematopoietic system (tissue-restricted mHags) such as HA-1 and HA-2; and (3) leukemia antigens, including leukemia-specific antigens such as BCR-ABL in Philadelphia-chromosome–positive leukemia and over- or aberrantly expressed leukemia-associated antigens (LAAs) such as proteinase 3 (PR3), Wilms tumor 1 (WT1) and the preferentially expressed antigen of melanoma (PRAME). A number of studies have shown a temporal inverse relationship between circulating T cells directed against mHags or LAAs and minimal residual disease in patients with acute and chronic leukemia after allogeneic HSCT, supporting a role for these antigens in the GVL response.1,2 This review will encompass a bench to bedside approach evaluating strategies for active induction or passive transfer of tumor-specific T cells in patients with hematological malignancies.