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  • [Cancer Res.] Granzyme B PET Imaging as a Predictive Biomarker of Immunotherapy Response

    Massachusetts General Hospital / Umar Mahmood*

  • 출처
    Cancer Res.
  • 등재일
    2017 May 1
  • 저널이슈번호
    77(9):2318-2327. doi: 10.1158/0008-5472.CAN-16-3346.
  • 내용

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    Abstract

    While cancer immunotherapy can produce dramatic responses, only a minority of patients respond to treatment. Reliable response biomarkers are needed to identify responders, and conventional imaging modalities have not proved adequate. Here, we provide a preclinical proof of concept for the use of granzyme B, a downstream effector of tumoral cytotoxic T cells, as an early biomarker for tumors responding to immunotherapy. We designed novel PET imaging probes for the murine and human granzyme B isoforms that specifically and quantitatively bind granzyme B. Immunotherapy-treated mice were imaged prior to therapy-induced tumor volume reduction. Imaging distinguished treated responders from nonresponders with excellent predictive ability. To assess the clinical value of a granzyme B imaging paradigm, biopsy specimens from melanoma patients on checkpoint inhibitor therapy were analyzed. A marked differential in granzyme B expression was observed between treated responders and nonresponders. Additionally, our human probe was able to specifically detect granzyme B expression in human samples, providing a clear candidate for clinical application. Overall, our results suggest granzyme B PET imaging can serve as a quantitatively useful predictive biomarker for efficacious responses to cancer immunotherapy. 

     

    Author information

    Larimer BM1, Wehrenberg-Klee E1, Dubois F1, Mehta A1, Kalomeris T1, Flaherty K2,3, Boland G4, Mahmood U5.

    Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts.

    Department of Medicine, Harvard Medical School, Boston, Massachusetts.

    Department of Medical Oncology, Massachusetts General Hospital, Boston, Massachusetts.

    Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts.

    Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts. umahmood@mgh.harvard.edu. 

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