Photoimmunotheranostics of epithelioid sarcoma by targeting CD44 or EGFR

Jiefu Jin, James D. Barnett, Yelena Mironchik, John Gross, Hisataka Kobayashi, Adam Levin, Zaver M. Bhujwalla

Research output: Contribution to journalArticlepeer-review

Abstract

Epithelioid sarcoma (ES) is a rare soft tissue neoplasm with high recurrence rates. Wide surgical resection remains the only potential curative treatment. ES presents most commonly on the fingers, hands and forearm, making light-based cancer cell-targeted therapies such as near-infrared photoimmunotherapy (NIR-PIT) that is target-specific, but with limited penetration depth, suitable for ES treatment. We established that CD44 and EGFR were overexpressed in ES patient samples and in the VA-ES-BJ human ES cell line. NIR-PIT of VA-ES-BJ cells using antibody photosensitizer conjugates, prepared by conjugating a CD44 or EGFR monoclonal antibody to the photosensitizer IR700, confirmed that NIR-PIT with both conjugates resulted in cell death. Neither treatment with NIR light alone nor treatment with the conjugates but without NIR light were effective. CD44-IR700-PIT resulted in greater cell death than EGFR-IR700-PIT, consistent with the increased expression of CD44 by VA-ES-BJ cells. In tumors, EGFR-IR700 exhibited a higher tumor-to-normal ratio, as determined by in vivo fluorescence imaging, and a higher anti-tumor growth effect, compared to CD44-IR700. No antitumor effect of the EGFR antibody or the photosensitizer conjugate alone was observed in vivo. Our data support evaluating the use of EGFR-IR700-PIT in the management of ES for detecting and eliminating ES cells in surgical margins, and in the treatment of superficial recurrent tumors.

Original languageEnglish (US)
Article number101966
JournalTranslational Oncology
Volume45
DOIs
StatePublished - Jul 2024

Keywords

  • CD44
  • EGFR
  • Epithelioid sarcoma
  • Photoimmunotheranostics
  • Targeted therapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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