Candidate Tumor Antigens for T-cell Therapy After Allogeneic HCT
Theoretically, T-cell immunotherapy can be designed to target molecules that are expressed on chemotherapy and radiotherapy-resistant cancer cells, including cancer stem cells, thus eliminating the subset of tumor cells that is most likely to survive the intense conditioning given to allogeneic HCT recipients and result in relapse.[4–6] Ideally, tumor antigens targeted by T cells should be expressed only by the tumor to avoid on-target toxicity to healthy tissues; however, in practice, many candidate tumor antigens are overexpressed self antigens that are also present in normal tissues. Two broad classes of molecules are now being intensively investigated as targets for T-cell therapy. The first consists of peptide antigens that are processed from intracellular proteins expressed in the tumor, presented in association with MHC molecules and recognized by the ab T-cell receptor. The second class of molecules are cell surface molecules that can be targeted by synthetically designed receptors, which typically consist of a single-chain variable fragment from a monoclonal antibody linked to T-cell signaling moieties and are introduced into T cells as a transgene. Such chimeric antigen receptors (CARs) confer MHC-independent recognition of tumor cells and thus avoid the problem of MHC loss that has been shown to be a mechanism for tumor escape from T cells after allogeneic HCT and in other settings.
Expert Rev Hematol. 2012;5(4):409-425. © 2012 Expert Reviews Ltd.