BEST IN PHYSICS (THERAPY): Radio-Immunotherapydose-Painting with Survival Boost Using Checkpoint Inhibitors
S Yasmin-Karim1*, M Moreau2, N Bih3, J Wirtz4, W Ngwa5, (1) Harvard Medical School,Boston, MA, (2) Dana Farber Cancer Institute, Everett, MA, (3) Dana Farber Cancer Institute, Boston, MA, (4) University Of Ulm, Ulm, Germany, ,,(5) Brigham and Womens Hospital, Boston, MA
Presentations
TU-C-TRACK 6-7 (Tuesday, 7/27/2021) 1:00 PM - 2:00 PM [Eastern Time (GMT-4)]
Purpose: Abscopal responses during radiotherapy are rare, especially for immunologically cold tumors like Castration resistant prostate cancer. Here we investigate a new approach called radio-immunotherapy dose-painting (RAID), which specifically targets tumor sub-volumes with radiotherapy and in-situ delivered immunoadjuvant to boost abscopal responses. The study is conducted in metastatic castration-resistant prostate cancer animal model with and without check-point inhibitors.
Methods: Syngeneic murine model of castration registrant prostate adenocarcinoma (CRPA) was generated in both flanks of wild C57/BL6 background mice using androgen deprived TRAMP-C1 cell lines. The palpable sized tumor of one of the flanks was treated as four different randomized cohorts: control with no treatment, direct treatment with 5 Gy of radiation, intra-tumor treatment with Immunogenic Biomaterial (IBM) loaded with AntiCD40, and in combination. Tumor growth was measured on both sides. The highest responded treatment method (RT+IBM) was rechallenged by adding checkpoint inhibitors, AntiPD1 and CTLA4, for survival study. Checkpoint inhiitors were given in systemic doses for 3 consequent administrations. Image Guided Radiotherapy (IGRT) targeting tumor and tumor sub-volumes was administered with the small animal radiation research platform.
Results: We demonstrate that the RAID approach substantially boosts abscopal responses for prostate cancer. Adding checkpoint inhibitors with 5 Gy of IGRT+IBM, further increases the survival duration, where the combination treatment with (RT+IBM) demonstrates enhancement of abscopal effect (p<0.001) compares with only RT, and only IBM. Adding AntiPD-1 (p<0.001) and CTLA4 (p<0.01) with the combination of RT+IBM, show significant increase in the survival duration. whereas, AntiPD-1 shows the longest duration of survival (>250 days), compared to others (<50 days) for at least one third of the treated mice.
Conclusion: RAID with IBM represents a promising new approach to significantly boost abscopal response rates for immunologically cold tumors like prostate cancer. Moreover, Checkpoint inhibitors like AntiPD-1 can further boost treatment outcomes.
Handouts
Keywords
Treatment Techniques, Small Fields
Taxonomy
TH- Small Animal RT: Development (new technology and techniques)
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