Purpose: To investigate the impact of sustained delivery of an immunoadjuvant drug, anti-CD40 monoclonal antibody (Ab_CD40), compared to its single direct in-situ administration in preclinical studies for determining optimal delivery of treatment for metastatic pancreatic tumors.
Methods: Smart radiotherapy biomaterials (SRBs) were designed similar to currently used gold fiducials, but with smart polymers that can provide imaging contrast and containing similar amount of anti-CD40 that lead tumor regression in animals. C57BL6/Tac mice were subcutaneously injected with KPC cells on one flank to study: a) the release of a fluorescent monoclonal antibody (anti-CD40-AF750) for up to 12-days and b) abscopal effect and mice survival post treatment. A small animal radiation research platform (SARRP) was used to deliver 5Gy at the tumor site followed by either a) free intratumoral injection of Ab_CD40 and b) SRB_Ab_CD40 treatment. Tumor volume size, survival and Immune cell infiltrations in tumors were assessed and results compared for the free direct injection of Ab_CD40 versus the SRB_Ab_CD40 that affords sustained delivery.
Results: Results showed sustained presence of the anti-CD40 in the tumors treated with SRB_Ab_CD40. The results further showed significant increase in abscopal response rates for animals treated with SRB_Ab_CD40 (p < 0.001) compared to animals treated with direct injection. Moreover, significant increase in survival was also observed for the SRB_Ab_CD40 cohort (p < 0.01) compared to direct free injection. Significantly more CD8+ T-cells (p < 0.001) and CD4+ T-cells (p < 0.01) were observed to infiltrate the SRB_CD40_5Gy tumor compared to the cohort that received free injection of Ab_CD40_5Gy.
Conclusion: Sustained delivery of anti-CD40 with smart radiotherapy biomaterials was more effective in boosting abscopal response rates compared to direct intratumoral injection. This establishes additional potential advantage of using smart sustained delivery of immunotherapy to boost the immune-mediated abscopal effect to engender robust local and metastatic tumor kill.