Abstract
Adoptive transfer of antigen‐specific T‐cells has shown therapeutic successes in the treatment of tumors in patients with metastatic melanoma. Tumor antigen‐specific T‐lymphocytes, however, occur only at low frequencies in a small proportion of patients. This low T‐lymphocyte frequency together with the difficulties associated with in vitro generation of T‐lymphocytes specific for cancers other than melanoma hampers adoptive T cell therapy. To make adoptive T‐cell therapy more uniformly applicable, strategies were developed at transferring tumor‐specificity to primary human T‐lymphocytes via antibody (Ig) or T‐cell receptor (TCR) molecules. We exploited the selection power of phage display that allows for the testing of tens of billions of individual clones with a high‐throughput selection of Fabs with peptide/MHC complex binding capacity. Following in vitro selection, human “TCR‐like” Fab fragments have been functionally expressed on human T‐lymphocytes, resulting in MHC‐restricted, tumor‐specific lysis and cytokine production. Currently, we have extended our selections to a panel of class I and II MHC‐restricted MAGE and other tumor‐specific epitopes, and would like to propose that phage display represents a technology able to expand T‐cell therapy to numerous tumor types. © 2008 International Society for Advancement of Cytometry