Program Information
Subcutaneously Modulated Abscopal Response Therapy
S Yasmin-Karim1*, W Ngwa2 , (1) Brigham and Women's Hospital, Boston, Massachusetts, (2) Harvard Medical School, Boston, MA
Presentations
MO-DE-605-8 (Monday, July 31, 2017) 1:45 PM - 3:45 PM Room: 605
Purpose: We hypothesize that by 'smartly' treating a subcutaneous tumor during radiotherapy, you can generate a highly effective immune-mediated abscopal effect that kills the subcutaneous tumor cells as well as metastatic tumor cells that were not treated
Methods: A syngeneic murine model of pancreatic cancer (Panc02) was generated in C57/BL6 mice. An orthotopic tumor was generated as well as a subcutaneous tumor on the left flank of each mouse. The mice were randomized into different cohorts after the subcutaneous tumors became palpable. Cohort A mice had subcutaneous tumors treated only with 20 µg of the immuno-adjuvant CD40-mAb. Cohort B mice were treated similar to cohort A mice but the subcutaneous tumors were also irradiated using the Small Animal Radiation Research Platform (SARRP). Cohort C mice were not treated with either immunoadjuvant or radiation. All mice were sacrificed and tumors weighed 14 days after the treatment started and infiltrating populations of immune cells assessed as biomarkers of the abscopal effect. The study was repeated for mice with untreated tumors in the right flank (n=8 per cohort).
Results: Untreated orthotopic tumors of cohorts A and B mice showed 34% and 74% regression, respectively, compared to the control cohort C mice. Assessing immune cell infiltrate populations, cohort B mice had T-cells populations that were 1.1 and 2 times higher than the cohorts A and C mice, respectively. Even more robust abscopal responses were seen in mice with untreated right flank tumors, with almost complete suppression of untreated tumors.
Conclusion: These preliminary results validate our hypothesis. These remarkable findings suggest a new Subcutaneously Modulated Abscopal Response Therapy (SMART) approach for extending the use of radiotherapy to treatment of both local and metastatic disease, via subcutaneous tumor modulation. The results provide strong basis for further studies testing this approach in pancreatic and other tumor models
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