Development of a Novel Therapeutic Transporter to Treat Metastatic Cancers

There is critical need for therapeutic delivery devices that can be administered intravenously (IV), and effectively home to and deliver therapeutic agents to diseased tissues, while maintaining patient safety. Cytonus Therapeutics, in collaboration with UC San Diegoandapos;s Moores Cancer Center, has pioneered a unique, drug transporter system with potential to treat to a wide range of cancers including advanced-stage metastatic tumors. Our novel platform for therapeutic delivery is to genetically engineer mesenchymal stem cells (MSCs) with specific tumor trophic proteins and then gently remove the nucleus, thereby providing a highly unique, viable, and safe drug delivery vehicle (CargocytesTM). Cargocytes are viable for at least 3-5 days and show dramatically reduced lung trapping after IV administration resulting in substantially improved homing to inflamed tissues in vivo. Moreover, Cargocytes can be engineered to express chemoattractant receptors CXCR4, CCR2, and the endothelial adhesion molecule PSGL-1, to enhance therapeutic delivery to tumors in response to their cognate ligands SDF-1, CCL2, and P-selectin, commonly upregulate in tumors and metastatic tissues, respectively. Therefore, feasibility studies will be performed to determine if cargocytes genetically engineered to simultaneously express chemoattractant receptors (CXCR4, CCR2) and PSGL-1 (endothelial adhesion molecule) facilitate improved homing to tumors (Aim 1) and lung metastases (Aim 2) in the MMTV-PyMT preclinical animal model of metastatic breast cancer. This work is important because bioengineered cargocytes could serve as a new biotransporter device to deliver therapeutics to malignant tumors and systemic metastases and maintain a clinically-relevant safety profile. Such innovative drug delivery platforms like Cargocytes are sorely needed to advance treatments for cancer patients with metastatic disease.There is critical need for therapeutic transporters that can be administered intravenously  (IV), and effectively home to and deliver therapeutic agents to tumors and/or metastatic  sites, while maintaining patient safety. The objective of this Phase I application is to first  develop a clinical prototype of an enucleated cargocyte transporter and demonstrate its  ability to home to primary tumors and metastatic sites using an established, clinically  relevant mouse model of breast cancer.