Multistep process through which adenoviral vector vaccine overcomes anergy to tumor-associated antigens.

Blood
Yucheng TangAlbert B Deisseroth

Abstract

Our goal in the present work was to characterize the multiple steps involved in overcoming the anergy that exists in tumor hosts to tumor-associated antigen (TAA). Our studies showed that the subcutaneous injection of the Ad-sig-TAA/ecdCD40L vector resulted in secretion of the TAA/ecdCD40L protein for at least 10 days from infected cells. Binding of the TAA/ecdCD40L protein to dendritic cells (DCs) resulted in the induction of CCR-7 chemokine receptor expression and cytokine release. This was followed by migration of the DCs to regional lymph nodes. Tetramer staining, enzyme-linked immunospot (ELISPOT) assay, and cytotoxicity assay all showed that the Ad-sig-TAA/ecdCD40L vector increased the levels of splenic CD8(+) T cells specific for the 2 TAAs (human MUC1 [hMUC1] and HPV E7) tested. Vaccination with the Ad-sighMUC1/ecdCD40L vector suppressed the growth of hMUC1 antigen-positive tumor cells in 100% of the test mice that were previously anergic to the hMUC1 antigen. These data suggest that Ad-sig-TAA-ecd/ecdCD40L vector injections may be of value in treating the many epithelial malignancies in which TAA-like hMUC1 is overexpressed.

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Citations

May 16, 2009·Cancer Immunology, Immunotherapy : CII·Yu Cheng TangAlbert Deisseroth
Aug 30, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Hakan AkbulutAlbert Deisseroth
Mar 22, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Barbara-ann GuinnAlbert B Deisseroth
May 17, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Gi Won YeJeong-Im Sin
Jan 1, 2012·ISRN Veterinary Science·Peter HedlinScott Napper
Oct 11, 2008·Cancer Gene Therapy·B A Guinn, R Mulherkar
Dec 25, 2008·Expert Review of Anticancer Therapy·Jeong-Im Sin
Jan 8, 2009·Cardiovascular Research·Daniel E ConwayLarry V McIntire
Jan 24, 2014·Clinical and Vaccine Immunology : CVI·Sarah Mackenzie-DyckSylvia van Drunen Littel-van den Hurk
Apr 13, 2018·PloS One·Daniel Martinez-MarquezRodney A Stewart
Oct 4, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yucheng TangAlbert Deisseroth

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