An Antibody Fab Fragment-based Chimeric Antigen Receptor Could Efficiently Eliminate Human Thyroid Cancer Cells

摘要

Thyroid cancer remains a significant health problem worldwide. Traditional chemotherapy does generate long-term benefit but are usually accompanied by severe side effects. Immunotherapy by adoptive infusion of T cells is now an attractive alternative to chemotherapy. Chimeric antigen receptor engineered lymphocytes have produced tremendous clinical outcomes in treating leukemia or lymphoma, but not in solid tumors, which is in part due to the low affinity of single chain Fv fragment or the rapid loss of transfused T cells. In present research, we designed a novel Fab based chimeric antigen receptor, which inherits the advantages of Fab fragment as well as the natural TCR receptor. The novel Fab CAR could recognize the tumor antigens independent of MHC/peptide complex, and mimic the natural activation process of endogenous TCR, therefore extend the life span of CAR-engineered T cells and generate durable clinical effects.