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dc.contributor.author Morse, MA
dc.contributor.author Hobeika, AC
dc.contributor.author Osada, T
dc.contributor.author Berglund, P
dc.contributor.author Hubby, B
dc.contributor.author Negri, S
dc.contributor.author Niedzwiecki, D
dc.contributor.author Devi, GR
dc.contributor.author Burnett, BK
dc.contributor.author Clay, TM
dc.contributor.author Smith, J
dc.contributor.author Lyerly, HK
dc.coverage.spatial United States
dc.date.accessioned 2011-06-21T17:27:56Z
dc.date.issued 2010-09
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/20679728
dc.identifier 42672
dc.identifier.citation J Clin Invest, 2010, 120 (9), pp. 3234 - 3241
dc.identifier.uri http://hdl.handle.net/10161/4330
dc.description.abstract Therapeutic anticancer vaccines are designed to boost patients' immune responses to tumors. One approach is to use a viral vector to deliver antigen to in situ DCs, which then activate tumor-specific T cell and antibody responses. However, vector-specific neutralizing antibodies and suppressive cell populations such as Tregs remain great challenges to the efficacy of this approach. We report here that an alphavirus vector, packaged in virus-like replicon particles (VRP) and capable of efficiently infecting DCs, could be repeatedly administered to patients with metastatic cancer expressing the tumor antigen carcinoembryonic antigen (CEA) and that it overcame high titers of neutralizing antibodies and elevated Treg levels to induce clinically relevant CEA-specific T cell and antibody responses. The CEA-specific antibodies mediated antibody-dependent cellular cytotoxicity against tumor cells from human colorectal cancer metastases. In addition, patients with CEA-specific T cell responses exhibited longer overall survival. These data suggest that VRP-based vectors can overcome the presence of neutralizing antibodies to break tolerance to self antigen and may be clinically useful for immunotherapy in the setting of tumor-induced immunosuppression.
dc.format.extent 3234 - 3241
dc.language ENG
dc.language.iso en_US en_US
dc.relation.ispartof J Clin Invest
dc.relation.isversionof 10.1172/JCI42672
dc.subject Adult
dc.subject Aged
dc.subject Alphavirus
dc.subject Antibodies, Neutralizing
dc.subject Antibody-Dependent Cell Cytotoxicity
dc.subject Antigens, Neoplasm
dc.subject Carcinoembryonic Antigen
dc.subject Colorectal Neoplasms
dc.subject Female
dc.subject Genetic Vectors
dc.subject Humans
dc.subject Male
dc.subject Middle Aged
dc.subject Neoplasms
dc.subject Replicon
dc.subject T-Lymphocytes, Regulatory
dc.title An alphavirus vector overcomes the presence of neutralizing antibodies and elevated numbers of Tregs to induce immune responses in humans with advanced cancer.
dc.title.alternative en_US
dc.type Journal Article
dc.description.version Version of Record en_US
duke.date.pubdate 2010-9-0 en_US
duke.description.endpage 3241 en_US
duke.description.issue 9 en_US
duke.description.startpage 3234 en_US
duke.description.volume 120 en_US
dc.relation.journal Journal of Clinical Investigation en_US
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/20679728
pubs.issue 9
pubs.organisational-group /Duke
pubs.organisational-group /Duke/Institutes and Provost's Academic Units
pubs.organisational-group /Duke/Institutes and Provost's Academic Units/University Institutes and Centers
pubs.organisational-group /Duke/Institutes and Provost's Academic Units/University Institutes and Centers/Global Health Institute
pubs.organisational-group /Duke/School of Medicine
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments/Biostatistics & Bioinformatics
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments/Immunology
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Medicine
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Medicine/Medicine, Clinical Pharmacology
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Medicine/Medicine, Medical Oncology
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Pathology
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Surgery
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Surgery/Surgery, Surgical Oncology Molecular Theraputics
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Surgery/Surgery, Surgical Sciences
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers/Duke Cancer Institute
pubs.publication-status Published
pubs.volume 120
dc.identifier.eissn 1558-8238

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