Prostatic Acid Phosphatase (PAP) Antibodies to Treat Castration-Resistant Prostate Cancer

Area of Science:

• Oncology
• Cancer Therapeutics
• Molecular Biology

Background:

• Prostate cancer (PCa) is a leading cause of cancer death in men, with metastatic disease often progressing to castration-resistant prostate cancer (CRPC) despite androgen deprivation therapy (ADT).
• Effective treatments for metastatic CRPC (mCRPC) are limited, necessitating the identification of novel therapeutic targets expressed on cancer cells.
• Prostatic acid phosphatase (PAP), particularly its transmembrane form (TMPAP), is a potential target identified as being expressed in CRPC.

Purpose of the Study:

• To identify and validate actionable cell surface targets for novel therapies against metastatic castration-resistant prostate cancer (mCRPC).
• To evaluate the therapeutic potential of targeting transmembrane prostatic acid phosphatase (TMPAP) using a human anti-TMPAP monoclonal antibody (3D8-Ab) and antibody-drug conjugates (3D8-ADCs).

Main Methods:

• Development of a human anti-TMPAP monoclonal antibody (3D8-Ab).
• Evaluation of 3D8-Ab and 3D8-ADCs in a xenograft mouse model using human PCa cell line VCaP.
• Assessment of tumor size, volume, and animal survival following treatment.

Main Results:

• Treatment with either 3D8-Ab or 3D8-ADCs significantly reduced tumor size and volume in the xenograft model.
• Both antibody-based therapies led to increased survival rates in the treated animals.
• These findings validate TMPAP as a viable therapeutic target in CRPC models.

Conclusions:

• Targeting TMPAP with monoclonal antibodies, alone or conjugated to toxins, represents a promising therapeutic strategy for CRPC.
• The anti-TMPAP antibody 3D8 and its conjugates demonstrate significant anti-tumor activity in preclinical models.
• Further development of PAP-targeted therapies could offer new treatment options for patients with advanced prostate cancer.