Detection of PSMA expression on circulating tumor cells by blood-based liquid biopsy in prostate cancer

Authors

  • Santosh Gupta Translational Research and Assay Development, Epic Sciences, San Diego, California - USA
  • Luisa Fernandez Translational Research and Assay Development, Epic Sciences, San Diego, California - USA
  • David Bourdon Translational Research and Assay Development, Epic Sciences, San Diego, California - USA
  • Anis A Hamid Department of Medical Oncology, University of Melbourne, Melbourne, Victoria - Australia
  • Anupama Pasam Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria - Australia
  • Ernest Lam Translational Research and Assay Development, Epic Sciences, San Diego, California - USA
  • Rick Wenstrup Translational Research and Assay Development, Epic Sciences, San Diego, California - USA
  • Shahneen Sandhu Department of Medical Oncology, University of Melbourne, Melbourne, Victoria - Australia and Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria - Australia

DOI:

https://doi.org/10.33393/jcb.2024.2636

Keywords:

Circulating tumor cells, Liquid biopsy, mCRPC, Prostate-specific membrane antigen (PSMA)

Abstract

Background: For patients with mCRPC, PSMA-targeted radioligand treatment has significantly improved the clinical outcome. A blood-based liquid biopsy assay for recognizing PSMA protein expression on circulating tumor cells may be beneficial for better informing therapeutic decision-making and identifying the patients most likely to benefit from PSMA-targeted radioligand therapy.

Methods: Using high-throughput imaging and digital AI pathology algorithms, a four-color immunofluorescence assay has been developed to find PSMA protein expression on CTCs on a glass slide. Cell line cells (LNCaP/PC3s/22Rv1) spiked into healthy donor blood were used to study the precision, specificity, sensitivity, limit of detection, and overall accuracy of the assay. Clinical validation and low-pass whole-genome sequencing were performed in PSMA-PET-positive patients with high-risk mCRPC (N = 24) utilizing 3 mL of blood.

Results: The PSMA CTC IF assay achieved analytical specificity, sensitivity, and overall accuracy above 99% with high precision. In the clinical validation, 76% (16/21) of the cases were PSMA positive with CTC heterogeneity, and 88% (21/24) of the patients contained at least one conventional CTC per milliliter of blood. Thirty-six low-pass-sequenced CTCs from 11 individuals with mCRPC frequently exhibited copy number increases in AR and MYC and losses in RB1, PTEN, TP53, and BRCA2 locus.

Conclusions: The analytical validation utilizing Epic Sciences’ liquid biopsy CTC platform demonstrated the potential to detect PSMA protein expression in CTCs from patients with mCRPC. This assay is positioned as an effective research tool to evaluate PSMA expression, heterogeneity, and therapeutic response in many ongoing clinical studies to target tumors that express PSMA.

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Published

2024-02-21

How to Cite

Gupta, S., Fernandez, L., Bourdon, D., Hamid, A. A., Pasam, A., Lam, E., Wenstrup, R., & Sandhu, S. (2024). Detection of PSMA expression on circulating tumor cells by blood-based liquid biopsy in prostate cancer. Journal of Circulating Biomarkers, 13(1), 1–6. https://doi.org/10.33393/jcb.2024.2636

Issue

Section

Original research article
Received 2023-07-18
Accepted 2024-01-08
Published 2024-02-21

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