Generation and testing of clinical-grade exosomes for pancreatic cancer

Mayela Mendt; Sushrut Kamerkar; Hikaru Sugimoto; Kathleen M. McAndrews; Chia Chin Wu; Mihai Gagea; Sujuan Yang; Elena V.Rodriges Blanko; Qian Peng; Xiaoyan Ma; Joseph R. Marszalek; Anirban Maitra; Cassian Yee; Katayoun Rezvani; Elizabeth Shpall; Valerie S. LeBleu; Raghu Kalluri

doi:10.1172/jci.insight.99263

Generation and testing of clinical-grade exosomes for pancreatic cancer

Mayela Mendt, Sushrut Kamerkar, Hikaru Sugimoto, Kathleen M. McAndrews, Chia Chin Wu, Mihai Gagea, Sujuan Yang, Elena V.Rodriges Blanko, Qian Peng, Xiaoyan Ma, Joseph R. Marszalek, Anirban Maitra, Cassian Yee, Katayoun Rezvani, Elizabeth Shpall, Valerie S. LeBleu, Raghu Kalluri

Research output: Contribution to journal › Article › peer-review

503 Scopus citations

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.

Original language	English (US)
Journal	JCI Insight
Volume	3
Issue number	8
DOIs	https://doi.org/10.1172/jci.insight.99263
State	Published - Apr 19 2018

Keywords

Cancer gene therapy
Oncology

ASJC Scopus subject areas

General Medicine

MD Anderson CCSG core facilities

Flow Cytometry and Cellular Imaging Facility
Genetically Engineered Mouse Facility
High Resolution Electron Microscopy Facility
Research Animal Support Facility
Small Animal Imaging Facility

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10.1172/jci.insight.99263

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title = "Generation and testing of clinical-grade exosomes for pancreatic cancer",

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",

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year = "2018",

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doi = "10.1172/jci.insight.99263",

language = "English (US)",

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AU - Mendt, Mayela

AU - Kamerkar, Sushrut

AU - Sugimoto, Hikaru

AU - McAndrews, Kathleen M.

AU - Wu, Chia Chin

AU - Gagea, Mihai

AU - Yang, Sujuan

AU - Blanko, Elena V.Rodriges

AU - Peng, Qian

AU - Ma, Xiaoyan

AU - Marszalek, Joseph R.

AU - Maitra, Anirban

AU - Yee, Cassian

AU - Rezvani, Katayoun

AU - Shpall, Elizabeth

AU - LeBleu, Valerie S.

AU - Kalluri, Raghu

PY - 2018/4/19

Y1 - 2018/4/19

N2 - 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.

AB - 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.

KW - Cancer gene therapy

KW - Oncology

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Generation and testing of clinical-grade exosomes for pancreatic cancer

Abstract

Keywords

ASJC Scopus subject areas

MD Anderson CCSG core facilities

Access to Document

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