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

doi:10.1016/j.tranon.2024.101966

Photoimmunotheranostics of epithelioid sarcoma by targeting CD44 or EGFR

Transl Oncol. 2024 Apr 24:45:101966. doi: 10.1016/j.tranon.2024.101966. Online ahead of print.

Authors

Jiefu Jin¹, James D Barnett², Yelena Mironchik², John Gross³, Hisataka Kobayashi⁴, Adam Levin⁵, Zaver M Bhujwalla⁶

Affiliations

¹ Division of Cancer Imaging Research, The Russell H Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: jjin@jhmi.edu.
² Division of Cancer Imaging Research, The Russell H Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
³ Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁴ Laboratory of Molecular Theranostics, Molecular Imaging Branch, NCI/NIH, Bethesda, MD, USA.
⁵ Orthopaedic Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁶ Division of Cancer Imaging Research, The Russell H Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: zbhujwa1@jhmi.edu.

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.

Keywords: CD44; EGFR; Epithelioid sarcoma; Photoimmunotheranostics; Targeted therapy.