Abstract LB-067: Cargocytes: A novel cell therapy platform to drive anti-tumor immunity

Adoptive cell therapy has emerged as a powerful new tool to treat cancer and other diseases. However, the clinical utility of many cell-based therapies is limited by inadequate production of therapeutic factors, production of unwanted factors, unwanted engraftment into the tumor, and poor controllability resulting in poor pharmacokinetics. Genetic and bioengineering strategies can overcome many limitations, but modification of genomic DNA or the introduction of new genetic material into therapeutic cells raises substantial safety concerns, ultimately making FDA approval difficult. To address these limitations, we developed a novel platform for cell-based therapies in which any cell type, including immortalized cells, can be extensively engineered and loaded with therapeutic cargo, and then rendered safe for patient administration through removal of the nucleus. Enucleated cells (Cargocytes) retain many desired biologic functions (endogenous and engineered), such as viability up to 72 hours, retention of cell surface markers/proteins, secretion of bioactive molecules, robust in vitro and in vivo chemotaxis, and delivery of a wide range of cancer-fighting cargos. Using this technology, we demonstrate that Cargocytes derived from hTERT-immortalized mesenchymal stem cells (hTERT MSCs) and engineered to express therapeutic levels of IL-12 can potently activate an anti-tumor immune response in a preclinical mouse model of triple negative breast cancer. hTERT MSC-derived Cargocytes robustly delivered IL-12 to the tumor with definable pharmacokinetics, activated known IL-12 biomarkers, and induced infiltration of tumor-fighting immune cells that inhibited tumor growth and improved animal survival. In addition, co-administration of Cargocytes secreting IL-12 and anti-PD-L1 antibodies further improved animal survival without notable adverse events. Collectively, our findings indicate that Cargocytes provide a new means to deliver powerful immunomodulatory biologics to malignant tumors in a safe and controllable manner. The genetic tractability and excellent safety profile of the Cargoycte platform enables bioengineering of a wide range of designer therapeutics derived from genetically modified cells, immortalized stem cells, and even cancer cells, each with improved clinically relevant functions. Citation Format: Richard L. Klemke, Huawei Wang, Bei Liu, Christina Alarcon, Felicia Watson. Cargocytes: A novel cell therapy platform to drive anti-tumor immunity [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 LB-067.