Induction of tumor antigen-specific immunity in vivo by a novel vaccinia vector encoding safety-modified simian virus 40 T antigen

Evidence that simian virus 40 (SV40) is associated with human mesotheliomas, osteosarcomas, and brain tumors suggests that a recombinant vaccine directed against lethal cancers expressing SV40 T antigen (Tag) could have clinical utility. To address this potential need, we designed a novel vaccinia v...

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Bibliographic Details
Published in:JNCI : Journal of the National Cancer Institute Vol. 91; no. 2; p. 169
Main Authors: Xie, Y C, Hwang, C, Overwijk, W, Zeng, Z, Eng, M H, Mulé, J J, Imperiale, M J, Restifo, N P, Sanda, M G
Format: Journal Article
Language:English
Published: United States 20.01.1999
Subjects:
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - immunology
Antineoplastic Agents - pharmacology
Blotting, Western
Cancer Vaccines - chemical synthesis
Cancer Vaccines - immunology
Cancer Vaccines - pharmacology
Defective Viruses - genetics
Genetic Vectors
Humans
Neoplasms - immunology
Neoplasms - therapy
Recombinant Proteins - chemical synthesis
Recombinant Proteins - immunology
Recombinant Proteins - pharmacology
Reverse Transcriptase Polymerase Chain Reaction
Simian virus 40 - immunology
T-Lymphocytes - immunology
Tumor Cells, Cultured
Vaccinia virus - genetics
ISSN:0027-8874
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Summary:Evidence that simian virus 40 (SV40) is associated with human mesotheliomas, osteosarcomas, and brain tumors suggests that a recombinant vaccine directed against lethal cancers expressing SV40 T antigen (Tag) could have clinical utility. To address this potential need, we designed a novel vaccinia virus construct that encodes an SV40 Tag in which oncogenic domains were excluded and immunogenic domains were preserved. We named this recombinant construct vaccinia-encoding safety-modified SV40 Tag (vac-mTag). Purified vac-mTag was characterized by DNA sequencing, reverse transcription-coupled polymerase chain reaction, western blot analysis, and immunocytochemical techniques. Induction of Tag-specific immunity was examined by cytolytic T-cell assays, and the efficacy of vac-mTag in protecting animals against Tag-expressing tumors and in treating pre-established microscopic tumors was evaluated in vac-mTag-immunized BALB/c mice. The immune response elicited by vac-mTag in C57BL/6 and BALB/c mice included an SV40 Tag-specific cytolytic T-lymphocyte activity against syngeneic (identical genetic background) SV40 Tag-expressing tumor targets. Immunization of mice with a single dose of vac-mTag resulted in potent protection against subsequent challenge with a lethal mouse cancer expressing SV40 Tag. In addition, single-dose vac-mTag immunization coadministered with interleukin 2 produced a possible therapeutic effect against a preadministered microscopic (but lethal) burden of Tag-expressing tumor cells in vivo. vac-mTag induces an effective immune response in mice that is specific for a tumor-associated antigen. This response protects against a lethal tumor challenge and results in a possible therapeutic effect against Tag-expressing tumors in vivo. Thus, vac-mTag provides a new avenue for the development of therapies for human cancers thought to be associated with SV40.
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ISSN:0027-8874
DOI:10.1093/jnci/91.2.169