Using immunotherapy to enhance the response of a C3H mammary carcinoma to proton radiation

• DOI: 10.1080/0284186x.2023.2238550
• Publication Date: 2023-07-27T15:12:31Z
• Authors: Steffen Nielsen; Mateusz K. Sitarz; Priyanshu M. Sinha; Charlemagne A. Fo...; Morten Høyer; Brita S. Sørensen; Michael R. Horsman
• Keywords: Mammary carcinoma; Mammary tumor

The benefit of combining immunotherapy with photon irradiation has been shown pre-clinically and clinically. This current pre-clinical study was designed to investigate the anti-tumour action protons.Male CDF1 mice, a C3H mammary carcinoma inoculated on right rear foot, were locally irradiated single radiation doses when tumours reached 200mm3. Radiation delivered an 83-107MeV pencil scanning proton beam in centre 3 cm spread out Bragg peak. Following (day 0), mice injected intraperitoneal anti-CTLA-4, anti-PD-1, or anti-PD-L1 (10 mg/kg) twice weekly for two weeks. Endpoints tumour growth time (TGT3; reach times treatment volume) local control (percent showing at 90 days). A Student's T-test (tumour growth) Chi-squared test control) used statistical analysis; significance levels p < 0.05.Untreated had mean (± 1 S.E.) TGT3 4.6 days 0.4). None checkpoint inhibitors changed this TGT3. linear increase seen increasing (5-20 Gy), reaching 17.2 0.7) 20 Gy. Anti-CTLA-4 no effect up 15 Gy, but significantly enhanced Gy; being 23.0 1.3). Higher (35-60 Gy) investigated using assay. Logit analysis dose response curve, resulted TCD50 value (radiation causing 50% control; 95% confidence intervals) 48 Gy (44-53) only. decreased 43 (38-49) treated anti-CTLA-4. Neither anti-PD-1 nor affected control.Checkpoint irradiation. However, enhancement depended inhibitor dose.