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Critical Reviews™ in Immunology
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ISSN Imprimir: 1040-8401
ISSN En Línea: 2162-6472

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Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v27.i5.40
pages 451-462

PART V. Modulation of Antitumor Vaccine Strategies
Preclinical and Clinical Studies of Recombinant Poxvirus Vaccines for Carcinoma Therapy

Philip M. Arlen
Neogenix Oncology, Inc. Rockville; and Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1750, USA
James L. Gulley
Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1750, USA
Ravi A. Madan
Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1750, USA
James W. Hodge
Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1750, USA
Jeffrey Schlom
Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1750, USA

SINOPSIS

Tumor-associated antigens (TAAs) are by definition either weakly immunogenic or functionally nonimmunogenic. Vaccine strategies have been designed to present TAAs to the immune system that may result in far greater activation of T cells than that occurring naturally in the host. These strategies include (1) placing the gene coding for the tumor antigen into poxvirus vectors as a transgene; (2) using diversified prime-and-boost vaccine strategies employing two different types of poxvirus vectors; (3) using T−cell costimulation; and (4) using cytokines, including GM−CSF, as biologic adjuvants. Preclinical studies have been performed comparing the effects on induction of antigen-specific CD8 and CD4 T−cell responses using recombinant poxvirus vectors containing transgenes for a TAA and costimulatory molecules B7−1, ICAM−1, and LFA−3 (designated TRICOM). Antigen-specific T−cell responses were greatest in the group receiving the CEA-TRICOM vaccines and were shown to correlate with survival. We have now completed the first clinical trials with poxvirus vectors containing TRICOM, using the TAAs PSA, CEA, and MUC−1. In addition, clinical studies combining vaccines with radiation therapy, chemotherapy, and second-line hormone therapy have provided preliminary evidence of prolongation of time to disease progression and “antigen cascade” postvaccination.


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