A novel fully human antibody targeting extracellular domain of PSMA inhibits tumor growth in prostate cancer

Molecular Cancer Therapeutics Online Fir.. by Wu, J., Han, D., Shi, S., Zhang, Q... - 2h ago Preview

 
 
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Prostate cancer (PCa) is the most commonly diagnosed malignancy in men and the second leading cause of cancer-related death. It is of vital importance to develop new strategies for PCa therapy. PSMA (Prostate specific membrane antigen) is specifically expressed in PCa and the neo-vasculature of certain cancer types, thus is considered to be an ideal target for cancer therapy. In our previous study, we have obtained an PSMA specific single chain variable fragment (scFv), named gy1, from a large yeast-display naive human scFv library. In this study, we reconstructed the PSMA scFv into a fully human antibody (named PSMAb) and evaluated its characterization both in vitro and in vivo. We showed that PSMAb can specifically bind with and internalize into PSMA+ cells. The binding affinity of PSMAb is measured to be at nanomolar level, and PSMAb has very good thermostability. In vivo study showed that near infrared dye labeled PSMAb can specifically localize at PSMA+ tumors, and the application of PSMAb in vivo significantly inhibited the growth of PSMA+ tumors, but not PSMA- tumors. At the studied doses, no obvious toxicity was observed when applied in vivo, as shown by the relative liver and kidney function and normal structure of important organs, shown by HE staining. In addition, PSMAb may inhibit tumor growth through ADCC and CDC mechanisms. Our results indicated that the novel fully human antibody PSMAb deserve further study for PSMA targeted diagnosis and therapy for PCa and other cancer types with vascular PSMA expression.