For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
0
views
39
references
 Top references
cited by
15
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      202
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Antitumor effects of iPSC-based cancer vaccine in pancreatic cancer

      brief-report

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          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

          Abstract

          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.

          Related collections

          Most cited references39

          • Record: found
          • Abstract: found
          • Article: not found

          Cancer statistics, 2019

          Rebecca Siegel, Kimberly D Miller, Ahmedin Jemal (2019)
          Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data, available through 2015, were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data, available through 2016, were collected by the National Center for Health Statistics. In 2019, 1,762,450 new cancer cases and 606,880 cancer deaths are projected to occur in the United States. Over the past decade of data, the cancer incidence rate (2006-2015) was stable in women and declined by approximately 2% per year in men, whereas the cancer death rate (2007-2016) declined annually by 1.4% and 1.8%, respectively. The overall cancer death rate dropped continuously from 1991 to 2016 by a total of 27%, translating into approximately 2,629,200 fewer cancer deaths than would have been expected if death rates had remained at their peak. Although the racial gap in cancer mortality is slowly narrowing, socioeconomic inequalities are widening, with the most notable gaps for the most preventable cancers. For example, compared with the most affluent counties, mortality rates in the poorest counties were 2-fold higher for cervical cancer and 40% higher for male lung and liver cancers during 2012-2016. Some states are home to both the wealthiest and the poorest counties, suggesting the opportunity for more equitable dissemination of effective cancer prevention, early detection, and treatment strategies. A broader application of existing cancer control knowledge with an emphasis on disadvantaged groups would undoubtedly accelerate progress against cancer.
          Article 0 comments Cited 6544 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            Tumor Mutational Burden and Response Rate to PD-1 Inhibition

            Mark Yarchoan, Alexander Hopkins, Elizabeth M. Jaffee (2017)
            Article 0 comments Cited 1172 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden

              Zachary Chalmers, Caitlin Connelly, David Fabrizio … (2017)
              Background High tumor mutational burden (TMB) is an emerging biomarker of sensitivity to immune checkpoint inhibitors and has been shown to be more significantly associated with response to PD-1 and PD-L1 blockade immunotherapy than PD-1 or PD-L1 expression, as measured by immunohistochemistry (IHC). The distribution of TMB and the subset of patients with high TMB has not been well characterized in the majority of cancer types. Methods In this study, we compare TMB measured by a targeted comprehensive genomic profiling (CGP) assay to TMB measured by exome sequencing and simulate the expected variance in TMB when sequencing less than the whole exome. We then describe the distribution of TMB across a diverse cohort of 100,000 cancer cases and test for association between somatic alterations and TMB in over 100 tumor types. Results We demonstrate that measurements of TMB from comprehensive genomic profiling are strongly reflective of measurements from whole exome sequencing and model that below 0.5 Mb the variance in measurement increases significantly. We find that a subset of patients exhibits high TMB across almost all types of cancer, including many rare tumor types, and characterize the relationship between high TMB and microsatellite instability status. We find that TMB increases significantly with age, showing a 2.4-fold difference between age 10 and age 90 years. Finally, we investigate the molecular basis of TMB and identify genes and mutations associated with TMB level. We identify a cluster of somatic mutations in the promoter of the gene PMS2, which occur in 10% of skin cancers and are highly associated with increased TMB. Conclusions These results show that a CGP assay targeting ~1.1 Mb of coding genome can accurately assess TMB compared with sequencing the whole exome. Using this method, we find that many disease types have a substantial portion of patients with high TMB who might benefit from immunotherapy. Finally, we identify novel, recurrent promoter mutations in PMS2, which may be another example of regulatory mutations contributing to tumorigenesis. Electronic supplementary material The online version of this article (doi:10.1186/s13073-017-0424-2) contains supplementary material, which is available to authorized users.
              Article 0 comments Cited 1117 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                Edgar G. Engleman
                Joseph C. Wu
                Journal
                Journal ID (nlm-ta): Stem Cell Reports
                Journal ID (iso-abbrev): Stem Cell Reports
                Title: Stem Cell Reports
                Publisher: Elsevier
                ISSN (Electronic): 2213-6711
                Publication date PMC-release: 06 May 2021
                Publication date Collection: 08 June 2021
                Publication date (Electronic): 06 May 2021
                Volume: 16
                Issue: 6
                Pages: 1468-1477
                Affiliations
                [1 ]Stanford Cardiovascular Institute, Stanford University, Stanford, CA 94305, USA
                [2 ]Department of Medicine, Division of Cardiovascular Medicine, Stanford University, 265 Campus Drive, Stanford, CA 94305, USA
                [3 ]Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA
                [4 ]Department of Medicine, Division of Gastroenterology & Hepatology, Stanford University, Stanford, CA 94305, USA
                [5 ]Department of Genetics, Stanford University, Stanford, CA 94305, USA
                [6 ]Department of Comparative Medicine, Stanford University, Stanford, CA 94305, USA
                [7 ]Department of Pathology, Stanford University, Stanford, CA 94305, USA
                [8 ]Department of Surgery, Leiden University Medical Center, Leiden, ZA 2333, the Netherlands
                Author notes
                [∗ ]Corresponding author edgareng@ 123456stanford.edu
                [∗∗ ]Corresponding author joewu@ 123456stanford.edu
                Article
                Publisher Item ID: S2213-6711(21)00199-5
                DOI: 10.1016/j.stemcr.2021.04.004
                PMC ID: 8190592
                PubMed ID: 33961792
                SO-VID: dee15e77-7548-455b-bd86-c3bbd3db1f49
                Copyright © © 2021 The Authors
                License:

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 2 October 2020
                Date revision received : 8 April 2021
                Date accepted : 9 April 2021
                Categories
                Subject: Report

                Keywords: ipsc,cancer vaccine,ipsc-based cancer vaccine,pancreatic ductal adenocarcinoma,tumor-associated antigens
                Data availability:
                Keywords: ipsc, cancer vaccine, ipsc-based cancer vaccine, pancreatic ductal adenocarcinoma, tumor-associated antigens

                Comments

                Comment on this article

                scite_

                Similar content202

                See all similar

                Cited by15

                See all cited by

                Most referenced authors1,416

                See all reference authors