Autologous iPSC-Based Vaccines Elicit Anti-tumor Responses In Vivo

Nigel G Kooreman; Youngkyun Kim; Patricia E de Almeida; Vittavat Termglinchan; Sebastian Diecke; Ning-Yi Shao; Tzu-Tang Wei; Hyoju Yi; Devaveena Dey; Raman Nelakanti; Thomas P Brouwer; David T Paik; Idit Sagiv-Barfi; Arnold Han; Paul H A Quax; Jaap F Hamming; Ronald Levy; Mark M Davis; Joseph C Wu

doi:10.1016/j.stem.2018.01.016

Autologous iPSC-Based Vaccines Elicit Anti-tumor Responses In Vivo

Cell Stem Cell. 2018 Apr 5;22(4):501-513.e7. doi: 10.1016/j.stem.2018.01.016. Epub 2018 Feb 15.

Authors

Nigel G Kooreman¹, Youngkyun Kim², Patricia E de Almeida³, Vittavat Termglinchan³, Sebastian Diecke⁴, Ning-Yi Shao³, Tzu-Tang Wei³, Hyoju Yi², Devaveena Dey³, Raman Nelakanti³, Thomas P Brouwer¹, David T Paik³, Idit Sagiv-Barfi⁵, Arnold Han⁶, Paul H A Quax⁷, Jaap F Hamming⁷, Ronald Levy⁸, Mark M Davis⁹, Joseph C Wu¹⁰

Affiliations

¹ Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cardiovascular Institute of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Surgery, Leiden University Medical Center, Leiden 2333 ZA, the Netherlands.
² Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cardiovascular Institute of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA; Convergent Research Consortium for Immunologic Disease, Seoul St. Mary's Hospital, Catholic University of Korea, Seoul 06591, Korea.
³ Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cardiovascular Institute of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
⁴ Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Robert-Rossle Strasse 10, 13125 Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site, Berlin, Germany; Berlin Institute of Health (BIH), Berlin, Germany.
⁵ Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
⁶ Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; The Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
⁷ Department of Surgery, Leiden University Medical Center, Leiden 2333 ZA, the Netherlands.
⁸ Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: levy@stanford.edu.
⁹ Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; The Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: mmdavis@stanford.edu.
¹⁰ Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cardiovascular Institute of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: joewu@stanford.edu.

Abstract

Cancer cells and embryonic tissues share a number of cellular and molecular properties, suggesting that induced pluripotent stem cells (iPSCs) may be harnessed to elicit anti-tumor responses in cancer vaccines. RNA sequencing revealed that human and murine iPSCs express tumor-associated antigens, and we show here a proof of principle for using irradiated iPSCs in autologous anti-tumor vaccines. In a prophylactic setting, iPSC vaccines prevent tumor growth in syngeneic murine breast cancer, mesothelioma, and melanoma models. As an adjuvant, the iPSC vaccine inhibited melanoma recurrence at the resection site and reduced metastatic tumor load, which was associated with fewer Th17 cells and increased CD11b⁺GR1^hi myeloid cells. Adoptive transfer of T cells isolated from vaccine-treated tumor-bearing mice inhibited tumor growth in unvaccinated recipients, indicating that the iPSC vaccine promotes an antigen-specific anti-tumor T cell response. Our data suggest an easy, generalizable strategy for multiple types of cancer that could prove highly valuable in clinical immunotherapy.

Keywords: adjuvant therapy; breast cancer; immune profiling; immunotherapy; melanoma; mesothelioma; metastases; pluripotent stem cells; prophylactic vaccination; shared epitopes.

Publication types

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

MeSH terms

Animals
Breast Neoplasms / immunology*
Breast Neoplasms / therapy
Cancer Vaccines / immunology*
Female
Humans
Induced Pluripotent Stem Cells / cytology
Induced Pluripotent Stem Cells / immunology*
Melanoma / immunology*
Melanoma / therapy
Mesothelioma / immunology*
Mesothelioma / therapy
Mice

Substances

Cancer Vaccines

Abstract

Publication types

MeSH terms

Substances

Grants and funding