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Blood, 1 November 2004, Vol. 104, No. 9, pp. 2704-2713.
Prepublished online as a Blood First Edition Paper on July 6, 2004; DOI 10.1182/blood-2003-12-4319.


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GENE THERAPY

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

Yucheng Tang, Lixin Zhang, Jing Yuan, Hakan Akbulut, Jonathan Maynard, Phyllis-Jean Linton, and Albert Deisseroth

From the Sidney Kimmel Cancer Center, San Diego, CA.

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. (Blood. 2004;104:2704-2713)


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Your Ad here: optimizing adenoviral vector-based vaccines
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Blood 2004 104: 2612-2613. [Full Text] [PDF]



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