Engineered fragments of anti-PSMA antibodies and their use in immunotherapy of prostate cancer

Jakub Ptáček, Zora Nováková, Cyril Bařinka

Laboratory of Structural Biology, Institute of Biotechnology CAS, BIOCEV

 

Prostate-specific membrane antigen (PSMA) is an excellent biomarker for prostate cancer (PCa) imaging and therapy. In our ongoing efforts targeting PSMA, we have developed a new monoclonal antibody 5D3 with sub-nanomolar affinity for human PSMA. Next, we used protein engineering to construct single-chain variable fragment derivatives of 5D3 (5D3-scFv), optimized expression and purification protocols and verified their functionality in complementary in vitro assays. We are further extending our experimental approaches by exploiting the 5D3-scFv in immunological platforms including (i) the design of bispecific fusions that will engage effector immune cells (macrophages and T-cells); and (ii) construction of chimeric antigen receptors (CARs) to transduce T-cells. Both of these platforms will be then tested in vitro and in vivo for immunotherapy of PSMA-expressing tumor cells.