Targeted systemic therapy of prostate cancer with a monoclonal antibody to prostate-specific membrane antigen

Area of Science:

• Oncology
• Immunotherapy
• Radiopharmaceutical Therapy

Background:

• Hormonal therapy for metastatic prostate cancer is palliative, necessitating improved systemic treatments.
• Monoclonal antibodies (mAbs) offer targeted cancer therapy by focusing immune responses or delivering cytotoxic agents.
• Prostate-specific membrane antigen (PSMA) is a highly restricted prostate cancer cell surface antigen, ideal for targeted therapies.

Purpose of the Study:

• To evaluate the efficacy of J591, a humanized IgG monoclonal antibody targeting prostate-specific membrane antigen (PSMA).
• To assess the potential of J591 in delivering therapeutic payloads, including radiometals and cytotoxins, to prostate cancer cells.

Main Methods:

• Development of J591, a humanized IgG monoclonal antibody targeting the extracellular domain of PSMA.
• Phase I clinical studies utilizing J591 linked to beta-emitting radiometals (yttrium 90, lutetium 177) or a cytotoxin (DM1).
• Imaging studies to assess tumor targeting after administration of radiolabeled J591.

Main Results:

• J591 targets the extracellular domain of PSMA, a highly specific antigen on prostate cancer cells.
• The PSMA-antibody complex is rapidly internalized after binding.
• Imaging demonstrates excellent tumor targeting of radiolabeled J591 in patients.

Conclusions:

• J591 represents a promising targeted therapy for prostate cancer, with potential for repeated dosing.
• J591-based therapies, including radiopharmaceuticals and antibody-drug conjugates, are under active clinical investigation.
• Targeting PSMA with monoclonal antibodies offers a novel strategy to overcome limitations of current prostate cancer treatments.