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Analyses of Recombinant Vaccinia and Fowlpox Vaccine Vectors Expressing Transgenes for Two Human Tumor Antigens and Three Human Costimulatory Molecules
Purpose: The poor immunogenicity of tumor antigens and the antigenic heterogeneity of tumors call for vaccine strategies to enhance T-cell responses to multiple antigens. Two antigens expressed noncoordinately on most human carcinomas are carcinoembryonic antigen (CEA) and MUC-1. We report here the...
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Published in: | Clinical cancer research 2005-02, Vol.11 (4), p.1597-1607 |
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Main Authors: | , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
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Online Access: | Get full text |
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Summary: | Purpose: The poor immunogenicity of tumor antigens and the antigenic heterogeneity of tumors call for vaccine strategies to enhance
T-cell responses to multiple antigens. Two antigens expressed noncoordinately on most human carcinomas are carcinoembryonic
antigen (CEA) and MUC-1. We report here the construction and characterization of two viral vector vaccines to address these
issues.
Experimental Design: The two viral vectors analyzed are the replication-competent recombinant vaccinia virus (rV-) and the avipox vector, fowlpox
(rF-), which is replication incompetent in mammalian cells. Each vector encodes the transgenes for three human costimulatory
molecules (B7-1, ICAM-1, and LFA-3, designated TRICOM) and the CEA and MUC-1 transgenes (which also contain agonist epitopes). The vectors are designated rV-CEA/MUC/TRICOM and rF-CEA/MUC/TRICOM.
Results: Each of the vectors is shown to be capable of faithfully expressing all five transgenes in human dendritic cells (DC). DCs
infected with either vector are shown to activate both CEA- and MUC-1–specific T-cell lines to the same level as DCs infected
with CEA-TRICOM or MUC-1-TRICOM vectors. Thus, no evidence of antigenic competition between CEA and MUC-1 was observed. Human
DCs infected with rV-CEA/MUC/TRICOM or rF-CEA/MUC/TRICOM are also shown to be capable of generating both MUC-1- and CEA-specific
T-cell lines; these T-cell lines are in turn shown to be capable of lysing targets pulsed with MUC-1 or CEA peptides as well
as human tumor cells endogenously expressing MUC-1 and/or CEA.
Conclusion: These studies provide the rationale for the clinical evaluation of these multigene vectors in patients with a range of carcinomas
expressing MUC-1 and/or CEA. |
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ISSN: | 1078-0432 1557-3265 |
DOI: | 10.1158/1078-0432.CCR-04-1609 |