Targeting Alpha Fetoprotein With Tcr Engineered T Cells In Hcc

3051Background: Alpha fetoprotein (AFP), an oncofetal protein, is transcriptionally repressed after birth. Reappearance of AFP in adult circulation indicates liver regeneration, hepatitis, chronic liver diseases, or malignant growth. When AFP positive, expression in HCC tends to be very high and homogeneous, making it an attractive immunotherapy target. Methods: A TCR specific for the HLA-A2-resricted peptide AFP158-165 (FMNKFIYEI) was identified and engineered to generate a panel of 12 affinity-enhanced TCRs (KD: 79.5-0.31mM). One clone (10mM KD), demonstrating enhanced potency against AFP-expressing liver tumor cell lines and no response to normal hepatocytes, was selected. Molecular mapping of each position of the target peptide was performed; the generated binding motif was searched against the human genome, identifying 165 potentially reactive peptides, which were synthesized, loaded onto T2 cells, and tested for reactivity by AFP TCR engineered T cells (AFP-T). Results: No safety concerns were ident...