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  • [Clin Cancer Res.] T세포 활성반영 PET으로 면역치료최적화The Effectiveness of Checkpoint Inhibitor Combinations and Administration Timing Can Be Measured by Granzyme B PET Imaging.

    Massachusetts General Hospital / Mahmood U*

  • 출처
    Clin Cancer Res.
  • 등재일
    2019 Feb 15
  • 저널이슈번호
    25(4):1196-1205. doi: 10.1158/1078-0432.CCR-18-2407. Epub 2018 Oct 16.
  • 내용

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    Abstract
    PURPOSE:
    The lack of a timely and reliable measure of response to cancer immunotherapy has confounded understanding of mechanisms of resistance and subsequent therapeutic advancement. We hypothesized that PET imaging of granzyme B using a targeted peptide, GZP, could be utilized for early response assessment across many checkpoint inhibitor combinations, and that GZP uptake could be compared between therapeutic regimens and dosing schedules as an early biomarker of relative efficacy.

    EXPERIMENTAL DESIGN:
    Two models, MC38 and CT26, were treated with a series of checkpoint inhibitors. GZP PET imaging was performed to assess tumoral GZP uptake, and tumor volume changes were subsequently monitored to determine response. The average GZP PET uptake and response of each treatment group were correlated to evaluate the utility of GZP PET for comparing therapeutic efficacy.

    RESULTS:
    In both tumor models, GZP PET imaging was highly accurate for predicting response, with 93% sensitivity and 94% negative predictive value. Mean tumoral GZP signal intensity of treatment groups linearly correlated with percent response across all therapies and schedules. Moreover, GZP PET correctly predicted that sequential dose scheduling of PD-1 and CTLA-4 targeted therapies demonstrates comparative efficacy to concurrent administration.

    CONCLUSIONS:
    Granzyme B quantification is a highly sensitive and specific early measure of therapeutic efficacy for checkpoint inhibitor regimens. This work provides evidence that GZP PET imaging may be useful for rapid assessment of therapeutic efficacy in the context of clinical trials for both novel drugs as well as dosing regimens.

     


    Author information

    Larimer BM1, Bloch E1, Nesti S1, Austin EE1, Wehrenberg-Klee E1, Boland G2, Mahmood U3.
    1
    Center for Precision Imaging, Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts.
    2
    Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts.
    3
    Center for Precision Imaging, Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts. umahmood@mgh.harvard.edu.

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