Abstract 2175: Synthetic antigen receptor mesenchymal stem cells (SAR-MSCs) targeting perlecan for drug delivery to ovarian cancer

Abstract

Abstract Mesenchymal stem cells (MSCs) can be engineered with polymeric nanoparticles for tumor-targeted delivery of small molecule drugs. Such nano-engineered MSCs have demonstrated exciting anticancer activity in multiple ovarian cancer models. Despite significantly improved delivery of chemotherapeutics to tumor tissues, non-specific accumulation of MSCs in clearance organs remains a concern. Paralleling the concept of CAR-T cells, we advance here a strategy for synthetic modification of MSCs with antibodies targeting specific antigens overexpressed on cancer cells. Our approach consists of stably incorporating recombinant protein G (PG) on the surface of MSCs, followed by binding of a full-length IgG to the PG handle. Because protein G binds to the Fc region of IgG, antigen-binding affinity of the antibody is conserved. We have previously shown the overexpression of perlecan (HSPG2) on ovarian cancer cells and its correlation to poor patient survival. In the current study, we investigated the incorporation of anti-perlecan antibody on the surface of nano-engineered MSCs. The anti-perlecan IgG antibody was first derivatized with palmitic acid (PA), which was then used to insert PG on MSCs cell membrane. We characterized the PAPG derivative by LC/Q-TOF/MS. Flow cytometry and confocal microscopy were used to confirm the incorporation of fluorescently labeled PAPG handle on MSC surface. Similarly, the binding of fluorescently labeled anti-perlecan IgG to PAPG-functionalized MSCs was confirmed by flow cytometry. We are currently investigating the anticancer efficacy of paclitaxel-loaded, anti-perlecan SAR-MSCs using in vitro and mouse models of ovarian cancer. Citation Format: Susheel Kumar Nethi, Dristhi Sehgal, Shen Cheng, Jayanth Panyam, Swayam Prabha. Synthetic antigen receptor mesenchymal stem cells (SAR-MSCs) targeting perlecan for drug delivery to ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2175.