Anti-PSMA antibodies for therapeutic and diagnostic purposes

Prostate cancer has the highest incidence and the second highest mortality among men in industrial countries. To improve prognosis a combination of precise diagnosis of tumor stage and specifically designed treatment plans is required. Prostate-specific membrane antigen (PSMA) is highly expressed on prostate cancer cells. Its specific presence in primary, high-grade and androgen-independent prostate cancer tumors as well as in metastases predetermines PSMA as a prime tool for prostate cancer imaging and therapy. So far, three PSMA-targeted small molecules have been approved for imaging purposes and the first PSMA-targeted radioligand-therapy gained approval by the FDA and EMA in 2022. Although progress has been made in the past years, there is a continuous high need for new prostate-cancer-specific applications, such as antibody-based therapies and diagnostics.

Our humanized anti-PSMA antibody 5D3 recognizes native human PSMA and is derived from the parent murine anti-PSMA antibody reported previously¹. The therapeutic and imaging potential of 5D3 has been demonstrated in vitro and in vivo. It retains its superior properties, such as sub-nanomolar affinity and high specificityfor native PSMA as well as good thermal stability. In addition, it has low immunogenicity as the murine antibody constant regions and V framework are replaced by human sequences. Anticipated liabilities were removed to facilitate various applications. Its excellent binding properties make 5D3 a superior candidate for conjugation to a therapeutic or an imaging agent.

The humanized anti-PSMA antibody 5D3 is suitable for prostate cancer therapy or imaging after conjugation with a therapeutic payload (a drug for ADC, radioligand for radiotherapy, photosensitizer for photodynamic therapy, etc.) or an imaging agent. “Sister” antibodies 1A11 and 3F11¹ are available for use in an immunohistochemistry companion diagnostic kit.

Optimized for developability, binding affinity and conformational stability in vitro