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
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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