Details
- Autor(en) / Beteiligte
- Titel
- Multistep process through which adenoviral vector vaccine overcomes anergy to tumor-associated antigens
- Ist Teil von
- Blood, 2004-11, Vol.104 (9), p.2704-2713
- Ort / Verlag
- Washington, DC: Elsevier Inc
- Erscheinungsjahr
- 2004
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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)
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0006-4971eISSN: 1528-0020DOI: 10.1182/blood-2003-12-4319Titel-ID: cdi_proquest_miscellaneous_66994366
- Format
- –
- Schlagworte
- Adenoviridae - genetics, Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy, Animals, Antigens, Neoplasm - administration & dosage, Antigens, Neoplasm - genetics, Antigens, Neoplasm - immunology, Antineoplastic agents, Applied cell therapy and gene therapy, Biological and medical sciences, Cancer Vaccines - genetics, Cancer Vaccines - immunology, Cancer Vaccines - pharmacology, CD40 Ligand - genetics, CD40 Ligand - metabolism, CD40 Ligand - therapeutic use, CD8-Positive T-Lymphocytes - drug effects, CD8-Positive T-Lymphocytes - immunology, Cell Survival - drug effects, Chemotaxis - drug effects, Clonal Anergy - drug effects, Clonal Anergy - immunology, Cytokines - metabolism, Dendritic Cells - drug effects, Dendritic Cells - metabolism, Dendritic Cells - physiology, Genetic Vectors - therapeutic use, Humans, Immunotherapy, Medical sciences, Mice, Mice, Transgenic, Mucin-1 - administration & dosage, Mucin-1 - genetics, Mucin-1 - pharmacology, Neoplasms, Experimental - pathology, Neoplasms, Experimental - therapy, Oncogene Proteins, Viral - administration & dosage, Oncogene Proteins, Viral - genetics, Oncogene Proteins, Viral - pharmacology, Papillomaviridae, Peptide Fragments - administration & dosage, Peptide Fragments - genetics, Peptide Fragments - pharmacology, Pharmacology. Drug treatments, Receptors, CCR7, Receptors, Chemokine - biosynthesis, Recombinant Fusion Proteins - administration & dosage, Recombinant Fusion Proteins - genetics, Recombinant Fusion Proteins - pharmacology, Transfusions. Complications. Transfusion reactions. Cell and gene therapy