Show simple item record

dc.contributor.authorMulryan, Kate
dc.contributor.authorRyan, Matthew G
dc.contributor.authorMyers, Kevin A
dc.contributor.authorShaw, David M
dc.contributor.authorWang, Who W
dc.contributor.authorKingsman, Susan M
dc.contributor.authorStern, Peter L
dc.contributor.authorCarroll, Miles W
dc.date.accessioned2009-11-06T09:17:34Z
dc.date.available2009-11-06T09:17:34Z
dc.date.issued2002-10
dc.identifier.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.en
dc.identifier.issn1535-7163
dc.identifier.pmid12481437
dc.identifier.urihttp://hdl.handle.net/10541/85515
dc.description.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.
dc.language.isoenen
dc.subjectCancer Antigensen
dc.subjectCanceren
dc.subjectCultured Tumour Cellsen
dc.subjectBiologival Tumour Markersen
dc.subject.meshAnimals
dc.subject.meshAntigens, Neoplasm
dc.subject.meshBlotting, Western
dc.subject.meshCancer Vaccines
dc.subject.meshCell Separation
dc.subject.meshCloning, Molecular
dc.subject.meshElectrophoresis, Polyacrylamide Gel
dc.subject.meshFlow Cytometry
dc.subject.meshHumans
dc.subject.meshImmunotherapy
dc.subject.meshMelanoma, Experimental
dc.subject.meshMembrane Glycoproteins
dc.subject.meshMice
dc.subject.meshMice, Inbred BALB C
dc.subject.meshMice, Inbred C57BL
dc.subject.meshNeoplasms
dc.subject.meshSpleen
dc.subject.meshTime Factors
dc.subject.meshTransfection
dc.subject.meshTumor Cells, Cultured
dc.subject.meshTumor Markers, Biological
dc.subject.meshVaccinia virus
dc.titleAttenuated recombinant vaccinia virus expressing oncofetal antigen (tumor-associated antigen) 5T4 induces active therapy of established tumors.en
dc.typeArticleen
dc.contributor.departmentCancer Research United Kingdom Immunology Group, Paterson Institute for Cancer Research, Christie Hospital, Manchester, M20 9BX, United Kingdom.en
dc.identifier.journalMolecular Cancer Therapeuticsen
html.description.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.


This item appears in the following Collection(s)

Show simple item record