Multistep process through which adenoviral vector vaccine overcomes anergy to tumor-associated antigens
BLOOD, vol.104, no.9, pp.2704-2713, 2004 (SCI-Expanded, Scopus)
- Publication Type: Article / Article
- Volume: 104 Issue: 9
- Publication Date: 2004
- Doi Number: 10.1182/blood-2003-12-4319
- Journal Name: BLOOD
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
- Page Numbers: pp.2704-2713
- Ankara University Affiliated: Yes
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-sig-hMUC1/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 over-expressed. (C) 2004 by The American Society of Hematology.