Tumor-DNA Based Vaccines Fail to Induce Autoimmune Disease in Mice



InSug O-Sullivan1, *, Terry Lichtor2, Roberta Glick3, Edward P. Cohen4
1 Department of Medicine, Endocrinology, Diabetes & Metabolism, University of Illinois College of Medicine, Chicago, IL 60612, USA
2 Rush University Medical School, Chicago, IL 60612, USA
3 Mount Sinai Hospital, Rush University Medical School, Department of Neurosurgery and Anatomy and Cell Biology, University of Illinois College of Medicine, Chicago, IL 60612, USA
4 Department of Microbiology and Immunology, University of Illinois College of Medicine, Chicago, IL 60612, USA


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© 2010 Sullivan et al.;

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Department of Medicine, Endocrinology, Diabetes & Metabolism, University of Illinois College of Medicine, 612 CMW (MC/ 640), Chicago, IL 60612, USA; Tel: 312-569-6594; Fax: 312-569-8114; E-mail: insug@uic.edu


Abstract

Allogeneic cellular cancer vaccines that express tumor antigens specified by tumor-DNA have been found to be effective in the treatment of mice with intracerebral breast cancer, a metastasis model system. The vaccines were prepared by the transfer of genomic DNA from a spontaneously arising adenocarcinoma of the mammary gland into a mouse fibroblast cell line (LM). The immunity in tumor-bearing mice treated by immunization with the DNA-based vaccines was specific for the type of tumor from which the DNA was obtained. It was driven mainly by CD8+ T-cells. Here, we present data indicating that animals receiving the therapeutic vaccines failed to exhibit signs of autoimmunity, as indicated by an examination of various H/E stained organs and tissues including brain for infiltrating inflammatory cells and by the absence of serum anti-nuclear antibody (ANA) in the immunized mice. In addition, tumors derived from the vaccine itself failed to develop in immune-competent tumor-free mice injected with the non-irradiated allogeneic vaccines alone.

Keywords: Immunotherapy, Metastasis, Breast Cancer, Autoimmunity.