Review Article: Untapped Potential: Peptide Ligands as Guides for Engineered T Cells

The seminal studies of the late Prof. Zelig Eshhar, the creator of "T-bodies," ushered in a new era of targeted cellular immunotherapy. As T-bodies came to be known as chimeric antigen receptors (CARs), the molecular requirements of these fusion proteins evolved, as did the technology enabling their expression in T cells. CAR T cells are fast becoming a mainstay therapy for hematological cancers such as multiple myeloma, and they are expanding into the field of solid cancer therapy. Nonetheless, one key barrier to their applicability is the limited number of tumor-specific targets that have been validated. An alternate approach which has until recently been almost totally bypassed is the use of peptide libraries to screen for and discover ligands capable of guiding the engineered T cells to novel cancer cell-restricted receptors. Peptides as targeting moieties have many advantages. This review summarizes the current state-of-the-art in the discovery and application of peptide-guided CAR-T cells in cancer immunotherapy.