Selection of human antibody fragments directed against tumor T-cell epitopes for adoptive T-cell therapy.

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