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Antitumor effects of iPSC-based cancer vaccine in pancreatic cancer.

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.
AuthorsXiaoming 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
JournalStem cell reports (Stem Cell Reports) Vol. 16 Issue 6 Pg. 1468-1477 (06 08 2021) ISSN: 2213-6711 [Electronic] United States
PMID33961792 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Chemical References
  • Antineoplastic Agents
  • Cancer Vaccines
Topics
  • Animals
  • Antineoplastic Agents (therapeutic use)
  • CD8-Positive T-Lymphocytes (immunology, metabolism)
  • Cancer Vaccines (immunology, metabolism, therapeutic use)
  • Carcinoma, Pancreatic Ductal (immunology, metabolism, therapy)
  • Cell Line, Tumor
  • Disease Models, Animal
  • Female
  • Humans
  • Immunologic Memory
  • Induced Pluripotent Stem Cells (immunology, metabolism)
  • Mice
  • Mice, Inbred C57BL
  • Pancreatic Neoplasms (immunology, therapy)
  • T-Lymphocytopenia, Idiopathic CD4-Positive (immunology, metabolism)
  • Transcriptome
  • Xenograft Model Antitumor Assays

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