Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Effective Combination Immunotherapy using Oncolytic Viruses to Deliver CAR Targets to Solid Tumors

Anthony K. Park, Yuman Fong, Nanhai G. Chen, Brook Jeang, Dileshni Tilakawardane, John P. Murad, Sang-In Kim, Jianming Lu, Sandra H. Thomas, Stephen J. Forman, Saul J. Priceman
doi: https://doi.org/10.1101/843052
Anthony K. Park
Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA 91010, USAIrell and Manella Graduate School of Biological Sciences, City of HopeDepartment of Surgery, City of Hope
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yuman Fong
Department of Surgery, City of Hope
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nanhai G. Chen
Department of Surgery, City of Hope
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Brook Jeang
Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA 91010, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dileshni Tilakawardane
Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA 91010, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
John P. Murad
Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA 91010, USAIrell and Manella Graduate School of Biological Sciences, City of Hope
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sang-In Kim
Department of Surgery, City of Hope
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jianming Lu
Department of Surgery, City of Hope
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sandra H. Thomas
Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA 91010, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Stephen J. Forman
Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA 91010, USADepartment of Immuno-Oncology, Beckman Research Institute of City of Hope
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Saul J. Priceman
Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA 91010, USADepartment of Immuno-Oncology, Beckman Research Institute of City of Hope
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: spriceman@coh.org
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

Chimeric antigen receptor (CAR)-engineered T cell therapy for solid tumors is limited by the lack of tumor-restricted and homogeneous expression of tumor antigens1,2. Therefore, we engineered an oncolytic virus to express a non-signaling, truncated CD19 (CD19t) protein for tumor-selective delivery, enabling targeting by CD19-specific CAR T cells. Infecting tumor cells with a chimeric oncolytic vaccinia virus coding for CD19t (OV19t) produced de novo CD19 surface-antigen expression prior to virus-mediated tumor lysis. Co-cultured CD19-CAR T cells secreted cytokines and elicited potent cytolytic activity against infected tumors. Using multiple mouse tumor models, intratumoral delivery of OV19t induced tumor expression of CD19t and improved tumor control following CD19-CAR T cell administration. CAR T cell–mediated tumor killing also promoted release of virus from dying tumor cells, which propogated tumor expression of CD19t. These data demonstrate a novel immunotherapy approach utilizing oncolytic viruses to promote de novo CAR T cell targeting of solid tumors.

One Sentence Summary We describe a novel and effective combination immunotherapy utilizing oncolytic viruses to deliver de novo cell surface expression of CD19 antigen promoting CD19-CAR T cell anti-tumor responses against solid tumors.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted November 16, 2019.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Effective Combination Immunotherapy using Oncolytic Viruses to Deliver CAR Targets to Solid Tumors
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
Share
Effective Combination Immunotherapy using Oncolytic Viruses to Deliver CAR Targets to Solid Tumors
Anthony K. Park, Yuman Fong, Nanhai G. Chen, Brook Jeang, Dileshni Tilakawardane, John P. Murad, Sang-In Kim, Jianming Lu, Sandra H. Thomas, Stephen J. Forman, Saul J. Priceman
bioRxiv 843052; doi: https://doi.org/10.1101/843052
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Effective Combination Immunotherapy using Oncolytic Viruses to Deliver CAR Targets to Solid Tumors
Anthony K. Park, Yuman Fong, Nanhai G. Chen, Brook Jeang, Dileshni Tilakawardane, John P. Murad, Sang-In Kim, Jianming Lu, Sandra H. Thomas, Stephen J. Forman, Saul J. Priceman
bioRxiv 843052; doi: https://doi.org/10.1101/843052

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Cancer Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (1647)
  • Biochemistry (2739)
  • Bioengineering (1907)
  • Bioinformatics (10243)
  • Biophysics (4183)
  • Cancer Biology (3218)
  • Cell Biology (4538)
  • Clinical Trials (135)
  • Developmental Biology (2840)
  • Ecology (4460)
  • Epidemiology (2041)
  • Evolutionary Biology (7231)
  • Genetics (5476)
  • Genomics (6813)
  • Immunology (2388)
  • Microbiology (7483)
  • Molecular Biology (2992)
  • Neuroscience (18584)
  • Paleontology (136)
  • Pathology (472)
  • Pharmacology and Toxicology (780)
  • Physiology (1149)
  • Plant Biology (2706)
  • Scientific Communication and Education (680)
  • Synthetic Biology (888)
  • Systems Biology (2846)
  • Zoology (468)