Antitumor effects of iPSC-based cancer vaccine in pancreatic cancer
Autor: | Binbin Chen, Aida Habtezion, Kerriann M. Casey, Bomi Lee, Nigel G. Kooreman, Xiaoming Ouyang, Yu Liu, Yang Zhou, Tzu-Tang Wei, Angela Zhang, Chun Liu, Joseph C. Wu, Edgar G. Engleman, Lin Wang, Jing Guo |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Induced Pluripotent Stem Cells pancreatic ductal adenocarcinoma Antineoplastic Agents CD8-Positive T-Lymphocytes Biology Cancer Vaccines Biochemistry Mice 03 medical and health sciences 0302 clinical medicine Immune system Report Cell Line Tumor Pancreatic cancer Genetics medicine Animals Humans Cytotoxic T cell tumor-associated antigens T-Lymphocytopenia Idiopathic CD4-Positive Induced pluripotent stem cell iPSC-based cancer vaccine iPSC Cancer Cell Biology medicine.disease Xenograft Model Antitumor Assays Mice Inbred C57BL Pancreatic Neoplasms Disease Models Animal 030104 developmental biology Cancer cell Cancer research Female Cancer vaccine cancer vaccine Transcriptome Immunologic Memory 030217 neurology & neurosurgery CD8 Carcinoma Pancreatic Ductal Developmental Biology |
Zdroj: | Stem Cell Reports |
ISSN: | 2213-6711 |
Popis: | Summary 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. Graphical abstract Highlights • The iPSC-based cancer vaccine prevents tumor growth in pancreatic cancer • The iPSC-based cancer vaccine induces cytotoxic antitumor T cell and B cell responses • The iPSC-based cancer vaccine reduces immune-suppressive Treg cells • iPSC-cancer signature genes are upregulated in mouse PDAC and human tumors In this article, Wu and colleagues demonstrate that an iPSC-based cancer vaccine, comprised of iPSCs and CpG, stimulated cytotoxic T cell and B cell responses, reduced immune-suppressive Treg cells, and prevented tumor formation in mice injected with pancreatic ductal adenocarcinoma (PDAC) cells. The “iPSC-cancer signature genes” are overexpressed among iPSC lines, PDAC cells, and multiple human cancers. These results support further studies of iPSC-based cancer vaccine for treatment of PDAC. |
Databáze: | OpenAIRE |
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