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JCI Insight. 2018 Apr 19;3(8). pii: 99263. doi: 10.1172/jci.insight.99263. eCollection 2018 Apr 19.

Generation and testing of clinical-grade exosomes for pancreatic cancer.

Author information

1
Department of Cancer Biology, Metastasis Research Center.
2
Department of Stem Cell Transplantation and Cellular Therapy.
3
Department of Genomic Medicine.
4
Department of Veterinary Medicine & Surgery.
5
Center for Co-Clinical Trials and Institute for Applied Cancer Science.
6
Departments of Pathology and Translational Molecular Pathology, Ahmad Center for Pancreatic Cancer Research, and.
7
Departments of Medical Melanoma and Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

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.

KEYWORDS:

Cancer gene therapy; Oncology

PMID:
29669940
PMCID:
PMC5931131
DOI:
10.1172/jci.insight.99263
[Indexed for MEDLINE]
Free PMC Article

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