Antitumor effects of iPSC-based cancer vaccine in pancreatic cancer

Xiaoming Ouyang; Yu Liu; Yang Zhou; Jing Guo; Tzu-Tang Wei; Chun Liu; Bomi Lee; Binbin Chen; Angela Zhang; Kerriann M Casey; Lin Wang; Nigel G Kooreman; Aida Habtezion; Edgar G Engleman; Joseph C Wu

doi:10.1016/j.stemcr.2021.04.004

Antitumor effects of iPSC-based cancer vaccine in pancreatic cancer

Stem Cell Reports. 2021 Jun 8;16(6):1468-1477. doi: 10.1016/j.stemcr.2021.04.004. Epub 2021 May 6.

Authors

Xiaoming Ouyang¹, Yu Liu¹, Yang Zhou¹, Jing Guo², Tzu-Tang Wei¹, Chun Liu¹, Bomi Lee³, Binbin Chen⁴, Angela Zhang¹, Kerriann M Casey⁵, Lin Wang¹, Nigel G Kooreman⁶, Aida Habtezion³, Edgar G Engleman⁷, Joseph C Wu⁸

Affiliations

¹ Stanford Cardiovascular Institute, Stanford University, Stanford, CA 94305, USA; Department of Medicine, Division of Cardiovascular Medicine, Stanford University, 265 Campus Drive, Stanford, CA 94305, USA.
² Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA.
³ Department of Medicine, Division of Gastroenterology & Hepatology, Stanford University, Stanford, CA 94305, USA.
⁴ Department of Genetics, Stanford University, Stanford, CA 94305, USA.
⁵ Department of Comparative Medicine, Stanford University, Stanford, CA 94305, USA.
⁶ Department of Surgery, Leiden University Medical Center, Leiden, ZA 2333, the Netherlands.
⁷ Department of Pathology, Stanford University, Stanford, CA 94305, USA. Electronic address: edgareng@stanford.edu.
⁸ Stanford Cardiovascular Institute, Stanford University, Stanford, CA 94305, USA; Department of Medicine, Division of Cardiovascular Medicine, Stanford University, 265 Campus Drive, Stanford, CA 94305, USA. Electronic address: joewu@stanford.edu.

Abstract

Induced pluripotent stem cells (iPSCs) and cancer cells share cellular similarities and transcriptomic profiles. Here, we show that an iPSC-based cancer vaccine, comprised of autologous iPSCs and CpG, stimulated cytotoxic antitumor CD8⁺ T cell effector and memory responses, induced cancer-specific humoral immune responses, reduced immunosuppressive CD4⁺ T regulatory cells, and prevented tumor formation in 75% of pancreatic ductal adenocarcinoma (PDAC) mice. We demonstrate that shared gene expression profiles of "iPSC-cancer signature genes" and others are overexpressed in mouse and human iPSC lines, PDAC cells, and multiple human solid tumor types compared with normal tissues. These results support further studies of iPSC vaccination in PDAC in preclinical and clinical models and in other cancer types that have low mutational burdens.

Keywords: cancer vaccine; iPSC; iPSC-based cancer vaccine; pancreatic ductal adenocarcinoma; tumor-associated antigens.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / therapeutic use
CD8-Positive T-Lymphocytes / immunology*
CD8-Positive T-Lymphocytes / metabolism
Cancer Vaccines / immunology*
Cancer Vaccines / metabolism
Cancer Vaccines / therapeutic use
Carcinoma, Pancreatic Ductal / immunology*
Carcinoma, Pancreatic Ductal / metabolism
Carcinoma, Pancreatic Ductal / therapy
Cell Line, Tumor
Disease Models, Animal
Female
Humans
Immunologic Memory
Induced Pluripotent Stem Cells / immunology*
Induced Pluripotent Stem Cells / metabolism
Mice
Mice, Inbred C57BL
Pancreatic Neoplasms / immunology*
Pancreatic Neoplasms / therapy
T-Lymphocytopenia, Idiopathic CD4-Positive / immunology*
T-Lymphocytopenia, Idiopathic CD4-Positive / metabolism
Transcriptome
Xenograft Model Antitumor Assays

Substances

Antineoplastic Agents
Cancer Vaccines

Abstract

Publication types

MeSH terms

Substances

Grants and funding