Abstract 557: EGFR-targeted mesenchymal stem cells for enhanced tumor retention and inhibition

Abstract

Abstract MSCs have been studied as gene therapy vehicles, and several preclinical and clinical studies support the use of genetically modified MSCs to deliver therapeutics to tumor tissues. We were one of the early groups to demonstrate that MSCs can be engineered to carry cytotoxic drugs by using nanoparticle-encapsulated form of the drug. However, tumor homing of MSCs is inefficient. We hypothesized that the targeting effectiveness of MSCs can be significantly improved by incorporating tumor-targeting ligands on the MSC surface that will allow for enhanced arrest and binding within the tumor tissue. In this study, we designed anti-EGFR Ab (cetuximab, Cmab) functionalized MSCs and studied the comparative therapeutic efficacy of paclitaxel-loaded, Cmab functionalized MSCs relative to that of paclitaxel-loaded, unfunctionalized MSCs. Cmab functionalized MSCs demonstrated improved binding to A549 adenocarcinoma cells. Mice bearing orthotopic A549 tumors were dosed i.v. with the various treatments. Similar to what we have shown previously, MSCs loaded with paclitaxel nanoparticles were effective in slowing tumor growth and improving the overall survival relative to that of other controls. However, the greatest inhibition of tumor growth was observed in mice that received anti-EGFR Ab functionalized, paclitaxel-loaded MSCs. Compared to a median survival of 21 days for saline and 27 days for paclitaxel-loaded MSC treated group and paclitaxel-loaded IgG functionalized MSCs, Cmab Ab functionalized, paclitaxel-loaded MSCs treated mice resulted in significantly improved median survival of 35 days (p<0.001). Biodistribution studies revealed a sixfold higher retention of functionalized MSCs when compared to unfunctionalized MSCs. These results demonstrate the potential for improved tumor targeting with EGFR-targeted MSCs. Citation Format: Susheelkumar Nethi, Shubhmita Bhatnagar, Xiaolei Li, Swayam Prabha. EGFR-targeted mesenchymal stem cells for enhanced tumor retention and inhibition [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 557.