Abstract 2110: Therapeutic intervention for pancreatic cancer using autologous exosomes
Authors: Saini Setua, Sheema Khan, Murali Yallapu, Sonam Kumari, Meena Jaggi, Subhash C. Chauhan
Journal: Cancer Research (2018)

Abstract Objective: Pancreatic cancer (PanCa) is the third deadliest cancer in United States with a poor survival rate. Despite extensive research efforts, there is not any substantial progress in cancer therapeutics due to impediments against intracellular drug delivery. Thus, novel delivery vehicles are required that are biocompatible and non-immunogenic. This is possible by utilizing an autologous biological material as delivery vehicles that can be applied as a personalized medicine. Towards this, our lab has optimized an exosomes based therapeutic approach, which utilizes exosomes isolated from the cultured tumor adjacent normal (NAT) fibroblast cells. We utilized this scaffold for safe and effective delivery of therapeutic payload. Methods: Following surgical resection, freshly collected, matched tumor adjacent normal tissues were utilized to isolate fibroblasts. Exosomes were purified from the isolated fibroblasts in presence of exosome-depleted FBS media. Physico-chemical characterization (DLS, TEM), presence of exosomal marker (CD63; immunoblotting), protein concentration (Bradford assay), cellular internalization (confocal microscopy) and miR-145 expression (qRT-PCR) in the exosomes were performed. Efficacy of exosomes to deliver therapeutics was investigated utilizing our recently identified drug, ormeloxifene (ORM). Drug encapsulation and loading efficiency was performed using UPLC. Functional assays, such as, proliferation were performed using clinically relevant PanCa cell lines (HPAF-II/AsPC-1). Results: NAT derived exosomes show effective size and zeta potential (size: 44.12 ± 0.89; Zeta potential: -14.9 mV), which is ideal for drug delivery purposes. The purification of exosomes was confirmed by analyzing the expression of exosomal markers, such as CD63. Immunofluorescence for CD63 expression confirmed the efficient delivery of exosomes in PanCa cells. Our results indicated high drug loading capacity of NAT derived exosomes as demonstrated though UPLC. ORM loaded exosome treatment efficiently delivered ORM into the cancer cells and inhibited tumorigenic features such as, proliferation of PanCa cells. Additionally, NAT derived exosomes showed enhanced expression of tumor suppressor microRNA, miR-145, suggestive of their therapeutic importance. We observed restoration of lost miR-145 levels in PanCa cells on incubation with NAT derived exosomes. This further indicates relevance for their utilization in the development of novel therapeutic modalities. Conclusion: Our observations offer importance of the utilization of NAT derived exosomes for personalized medicine as a therapeutic strategy in PanCa treatment. Citation Format: Saini Setua, Sheema Khan, Murali Yallapu, Sonam Kumari, Meena Jaggi, Subhash C. Chauhan. Therapeutic intervention for pancreatic cancer using autologous exosomes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2110.