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

By Mayela Mendt, S. Kamerkar, H. Sugimoto, Kathleen M. McAndrews, Chia-Chin Wu, Mihai Gagea, Sujuan Yang, E. R. Blanko, Q. Peng, Xiaoyan Ma and 7 more. JCI Insight, 2018

706 citations recorded by the source corpus.

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.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/31336c88c7cf7cf4bddd4b28f7f69040b34fc3f6

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. Valerie S. LeBleu
2. Raghu Kalluri
3. D. Hanahan

In Molecular Biology

1. Valerie S. LeBleu
2. Raghu Kalluri
3. M. Nieto
4. R. Weinberg
5. D. Hanahan
6. Zena Werb
7. Youhua Liu

Citations in the corpus

• The biology, function, and biomedical applications of exosomes (2020, positive): “Clinical-grade MSCderived exosomeswithKras siRNApayload (iExosomes) have been used to treat pancreatic cancer in multiple animal models (28, 35).”