Program Information
Priming the Abscopal Effect Using Radiotherapy Biomaterials Loaded with Immune-Adjuvants
M Moreau123*, S Yasmin-Karim23 , R Ashtaputre3 , W Ngwa1234 , (1) University of Massachusetts Lowell, Lowell, MA, (2) Brigham and Women's Hospital, Boston, Massachusetts, (3) Dana Farber Cancer Institute, Boston, MA, (4) Harvard Medical School, Boston, MA
Presentations
MO-DE-605-7 (Monday, July 31, 2017) 1:45 PM - 3:45 PM Room: 605
Purpose: To develop multi-functional radiotherapy biomaterials (MRBs), that can aid the host’s immune system to fight cancer cells in metastatic stage.
Methods: MRBs were designed similarly to currently use inert radiotherapy biomaterials (spacers, fiducials, beacons) but including a biodegradable polymer component loaded with FITC dye as a drug surrogate. Sustained release of 1% FITC dye from these SRBs (length 3mm) was investigated in PBS and 0.2% Agar gel using a micro-plate reader. Subsequently, the FITC dye was replaced with the immune-adjuvant CD40 mAb and implanted using a brachytherapy needle in subcutaneous lung tumors in mice. The mice were divided into 6 cohorts where 3 cohorts were irradiated at 5Gy and the other 3 were not. Two cohorts had no treatment, two had intra-tumoral injection of CD40 mAb, and two had MRBs (loaded with the same concentration and amount of CD40 mAb). Only the right flank tumors received treatment and not the left ones. The tumor size was measured using a vernier caliper. Radiation and imaging were performed using a small animal radiation research platform (SARRP) at 65 kVp.
Results: Results showed sustained release of the FITC dye from the SRB over many days, with faster release in PBS compared to gel, as would be expected. Remarkably, the preliminary results in mice showed major reduction of the tumor size for cohort with MRB loaded with immune-adjuvant.
Conclusion: These promising results justify further investigations to optimize the design of our SRBs to radiotherapy schedules for amplifying both local and remote (metastatic) tumor cell kill. If effectively translated to the clinic, this could come at virtually no additional inconvenience to patients where the MRBs could simply replace currently used inert radiotherapy biomaterials. Sustained in-situ delivery of immune-adjuvants from such MRBs would also minimize systemic/overlapping toxicities, which are a major limitations to competing approaches.
Contact Email: