Generation and testing of clinical-grade exosomes for pancreatic cancer

TLDR

Exosomes are extracellular vesicles that can transfer genetic material, such as siRNA, to cancer cells. The study reports a bioreactor‑based, large‑scale production of clinical‑grade exosomes under GMP standards. The authors established a GMP bioreactor SOP to generate engineered iExosomes targeting oncogenic Kras and conducted studies on shelf life, biodistribution, toxicology, and combination‑therapy efficacy. In vitro and in vivo experiments showed that GMP iExosomes suppress oncogenic Kras, increase survival in pancreatic cancer mouse models, and demonstrate the feasibility of clinical‑grade exosome therapies.

Abstract

Exosomes are extracellular vesicles produced by all cells with a remarkable ability to efficiently transfer genetic material, including exogenously loaded siRNA, to cancer cells. Here, we report on a bioreactor-based, large-scale production of clinical-grade exosomes employing good manufacturing practice (GMP) standards. A standard operating procedure was established to generate engineered exosomes with the ability to target oncogenic Kras (iExosomes). The clinical-grade GMP iExosomes were tested in multiple in vitro and in vivo studies to confirm suppression of oncogenic Kras and an increase in the survival of several mouse models with pancreatic cancer. We perform studies to determine the shelf life, biodistribution, toxicology profile, and efficacy in combination with chemotherapy to inform future clinical testing of GMP iExosomes. Collectively, this report illustrates the process and feasibility of generating clinical-grade exosomes for various therapies of human diseases.