A novel alphavirus vaccine encoding prostate-specific membrane antigen elicits potent cellular and humoral immune responses.

A novel alphavirus vaccine encoding prostate-specific membrane antigen elicits potent cellular and humoral immune responses. Research Abstract Details 

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A novel alphavirus vaccine encoding prostate-specific membrane antigen elicits potent cellular and humoral immune responses. Abstract Text:

Robert J Durso,Sofija Andjelic,Jason P Gardner,Dennis J Margitich,Gerald P Donovan,Robert R Arrigale,Xinning Wang,Maureen F Maughan,Todd L Talarico,Robert A Olmsted,Warren D W Heston,Paul J Maddon,William C Olson,

PURPOSE: Prostate-specific membrane antigen (PSMA) is an attractive target for active immunotherapy. Alphavirus vaccines have shown promise in eliciting immunity to tumor antigens. This study investigated the immunogenicity of alphavirus vaccine replicon particles (VRP) that encode PSMA (PSMA-VRP). EXPERIMENTAL DESIGN: Cells were infected with PSMA-VRP and evaluated for PSMA expression and folate hydrolase activity. Mice were immunized s.c. with PSMA-VRP or purified PSMA protein. Sera, splenocytes, and purified T cells were evaluated for the magnitude, durability, and epitope specificity of the anti-PSMA response. Antibodies were measured by flow cytometry, and cellular responses were measured by IFN-gamma enzyme-linked immunospot and chromium release assays. Cellular responses in BALB/c and C57BL/6 mice were mapped using overlapping 15-mer PSMA peptides. A Good Laboratory Practice-compliant toxicology study was conducted in rabbits. RESULTS: PSMA-VRP directed high-level expression of active PSMA. Robust T-cell and B-cell responses were elicited by a single injection of 2 x 10(5) infectious units, and responses were boosted following repeat immunizations. Anti-PSMA responses were detected following three immunizations with 10(2) infectious units and increased with increasing dose. PSMA-VRP was more immunogenic than adjuvanted PSMA protein. Responses to PSMA-VRP were characterized by Th-1 cytokines, potent CTL activity, and IgG2a/IgG2b antibodies. T-cell responses in BALB/c and C57BL/6 mice were directed toward different PSMA peptides. Immunogenic doses of PSMA-VRP were well tolerated in mice and rabbits. CONCLUSIONS: PSMA-VRP elicited potent cellular and humoral immunity in mice, and specific anti-PSMA responses were boosted on repeat dosing. PSMA-VRP represents a promising approach for immunotherapy of prostate cancer.

A novel alphavirus vaccine encoding prostate-specific membrane antigen elicits potent cellular and humoral immune responses. Publishing Authors By Initials

RJ Durso,S Andjelic,JP Gardner,DJ Margitich,GP Donovan,RR Arrigale,X Wang,MF Maughan,TL Talarico,RA Olmsted,WD Heston,PJ Maddon,WC Olson,

For similar cells: blood cells: leukocytes: leukocytes, mononuclear: lymphocytes: t-lymphocytes: cd8-positive t-lymphocytes: t-lymphocytes, cytotoxic research abstracts see: cells: blood cells: leukocytes: leukocytes, mononuclear: lymphocytes: t-lymphocytes: cd8-positive t-lymphocytes: t-lymphocytes, cytotoxic research

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A novel alphavirus vaccine encoding prostate-specific membrane antigen elicits potent cellular and humoral immune responses. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Clinical cancer research : an official journal of

VOLUME: 13

Page Numbers: 3999-4008

Journal Abbreviation: Clin. Cancer Res.

ISSN: 1078-0432

DAY: 1

MONTH: Jul

YEAR: 2007

A novel alphavirus vaccine encoding prostate-specific membrane antigen elicits potent cellular and humoral immune responses. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9502500

A novel alphavirus vaccine encoding prostate-specific membrane antigen elicits potent cellular and humoral immune responses. Keywords Mesh Terms:

KEYWORDS: T-Lymphocytes, Cytotoxic

MESH TERMS: metabolism

Chemical & Substance for Abstract: A novel alphavirus vaccine encoding prostate-specific membrane antigen elicits potent cellular and humoral immune responses. Information

Substance Name: glutamate carboxypeptidase II, human

Registry Number: EC 3.4.17.21

Grant and Affiliation Information for A novel alphavirus vaccine encoding prostate-specific membrane antigen elicits potent cellular and humoral immune responses.

AFFILIATION: Progenics Pharmaceuticals, Inc., Tarrytown, New York 10591, USA.

Country: United States

AGENCY: United States NCI

GRANT: CA95928

ACRONYM: CA

MEDLINETA: Clin Cancer Res

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