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Critical Reviews™ in Immunology

ISSN for PRINT: 1040-8401

Institutional price:	$831.00
Issues per year:	6

Best Paper Award Selection - Editorial Board Site

2007, Volume27

97 pages

Issue price - $153.00

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

Philip M. Arlen
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

ABSTRACT

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.