Attenuated recombinant vaccinia virus expressing oncofetal antigen (tumor-associated antigen) 5T4 induces active therapy of established tumors.
Ryan, Matthew G
Myers, Kevin A
Shaw, David M
Wang, Who W
Kingsman, Susan M
Stern, Peter L
Carroll, Miles W
AffiliationCancer Research United Kingdom Immunology Group, Paterson Institute for Cancer Research, Christie Hospital, Manchester, M20 9BX, United Kingdom.
MetadataShow full item record
AbstractThe human oncofetal antigen 5T4 (h5T4) is a transmembrane glycoprotein overexpressed by a wide spectrum of cancers, including colorectal, ovarian, and gastric, but with a limited normal tissue expression. Such properties make 5T4 an excellent putative target for cancer immunotherapy. The murine homologue of 5T4 (m5T4) has been cloned and characterized, which allows for the evaluation of immune intervention strategies in "self-antigen" in vivo tumor models. We have constructed recombinant vaccinia viruses based on the highly attenuated and modified vaccinia virus ankara (MVA strain), expressing h5T4 (MVA-h5T4), m5T4 (MVA-m5T4), and Escherichia coli LacZ (MVA-LacZ). Immunization of BALB/c and C57BL/6 mice with MVA-h5T4 and MVA-m5T4 constructs induced antibody responses to human and mouse 5T4, respectively. C57BL/6 and BALB/c mice vaccinated with MVA-h5T4 were challenged with syngeneic tumor line transfectants, B16 melanoma, and CT26 colorectal cells that express h5T4. MVA-h5T4-vaccinated mice showed significant tumor retardation compared with mice vaccinated with MVA-LacZ or PBS. In active treatment studies, inoculation with MVA-h5T4 was able to treat established CT26-h5T4 lung tumor and to a lesser extent B16.h5T4 s.c. tumors. Additionally, when C57BL/6 mice vaccinated with MVA-m5T4 were challenged with B16 cells expressing m5T4, resulting growth of the tumors was significantly retarded compared with control animals. Furthermore, mice vaccinated with MVA-m5T4 showed no signs of autoimmune toxicity. These data support the use of MVA-5T4 for tumor immunotherapy.
CitationAttenuated recombinant vaccinia virus expressing oncofetal antigen (tumor-associated antigen) 5T4 induces active therapy of established tumors. 2002, 1 (12):1129-37 Mol. Cancer Ther.
JournalMolecular Cancer Therapeutics
- Active treatment of murine tumors with a highly attenuated vaccinia virus expressing the tumor associated antigen 5T4 (TroVax) is CD4+ T cell dependent and antibody mediated.
- Authors: Harrop R, Ryan MG, Myers KA, Redchenko I, Kingsman SM, Carroll MW
- Issue date: 2006 Sep
- 5T4-modified vaccinia ankara: progress in tumor-associated antigen-based immunotherapy.
- Authors: Amato RJ
- Issue date: 2007 Sep
- 5T4-modified vaccinia Ankara: progress in tumor-associated antigen-based immunotherapy.
- Authors: Amato RJ
- Issue date: 2010 Feb
- Vaccination of colorectal cancer patients with modified vaccinia Ankara delivering the tumor antigen 5T4 (TroVax) induces immune responses which correlate with disease control: a phase I/II trial.
- Authors: Harrop R, Connolly N, Redchenko I, Valle J, Saunders M, Ryan MG, Myers KA, Drury N, Kingsman SM, Hawkins RE, Carroll MW
- Issue date: 2006 Jun 1
- Combination of intratumoral injections of vaccinia virus MVA expressing GM-CSF and immunization with DNA vaccine prolongs the survival of mice bearing HPV16 induced tumors with downregulated expression of MHC class I molecules.
- Authors: Nemeckova S, Smahel M, Hainz P, Mackova J, Zurkova K, Gabriel P, Indrova M, Kutinova L
- Issue date: 2007