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Analyzing Tumor and Tissue Distribution of Target Antigen Specific Therapeutic Antibody
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Systematic profiling of tumor-associated antigen expression for antibody-drug conjugate in prostate cancer.

Yelin Mulati1,2,3,4, Qi Shen1,2,3,4, Yuke Chen1,2,3,4

  • 1Department of urology, Peking University First Hospital, Beijing, China.

Prostate Cancer and Prostatic Diseases
|December 24, 2025
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B7H3, STEAP1, and PSMA show consistent expression in prostate cancer lesions, making them promising targets for antibody-drug conjugate therapies. These findings highlight the dynamic nature of tumor-associated antigen expression for targeted treatment strategies.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Immunotherapy

Background:

  • Prostate cancer (PCa) treatment can be improved by understanding tumor-associated antigen (TAA) expression.
  • Antibody-drug conjugates (ADCs) are a promising targeted therapy for PCa.
  • Characterizing TAAs in primary lesions (PL) and bone metastatic lesions (BML) is crucial for ADC development.

Purpose of the Study:

  • To compare the expression profiles of key TAAs (HER2, NECTIN4, TROP2, PSMA, TF, STEAP1, B7H3) in PL and BML of prostate cancer.
  • To identify optimal TAA targets for antibody-drug conjugate (ADC) therapy in PCa.

Main Methods:

  • Mass spectrometry (MS) and immunohistochemistry (IHC) were employed to analyze TAA expression in matched PL and BML samples from 27 PCa patients.
  • An independent cohort of 100 PL and 49 BML samples was used for IHC validation.
  • Quantitative IHC methods, including H-score and normalized membrane ratio (NMR), were utilized.

Main Results:

  • B7H3, STEAP1, and PSMA demonstrated high and stable expression in both PL and BML.
  • STEAP1, B7H3, and PSMA showed high expression rates in BML, with STEAP1 and B7H3 exhibiting homogeneous membranous patterns.
  • Combinations of B7H3, STEAP1, and PSMA achieved over 85% expression coverage in BML.

Conclusions:

  • B7H3, STEAP1, and PSMA are identified as predominant targets for ADC therapy in both primary and bone metastatic prostate cancer lesions.
  • The study underscores the heterogeneity of TAA expression in PCa, informing the strategic integration of ADC therapies.
  • Findings provide valuable insights for developing more effective targeted treatment strategies for advanced prostate cancer.