Herpes simplex virus (HSV)-mediated ICAM-1 gene transfer abrogates tumorigenicity and induces anti-tumor immunity.
Michael I. D’Angelica,Cindy Tung,Peter J. Allen,Marc W. Halterman,Keith A. Delman,Thomas Delohery,David S. Klimstra,Michael Brownlee,Howard J. Federoff,Yuman Fong +9 more
TL;DR: Increased tumor expression of ICAM-1 represents a promising immune anti-cancer strategy and HSV amplicon-mediated gene transfer is an efficient method for modifying the cell surface expression of adhesion molecules.
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Abstract: Costimulatory and cellular adhesion molecules are thought to be essential components of antigen presentation in the immune response to cancer. The current studies examine gene transfer utilizing herpes viral amplicon vectors (HSV) to direct surface expression of adhesion molecules, and specifically evaluate the potential of a tumor-expressing intercellular adhesion molecule-1 (ICAM-1) to elicit an anti-tumor response. The human ICAM-1 (hICAMI) gene was inserted into an HSV amplicon vector and tested in a transplantable rat hepatocellular carcinoma and in a human colorectal cancer cell line. Cell surface ICAM-1 expression was assessed by flow cytometry. Lymphocyte binding to HSV-hICAM1-transduced cells was compared with that to cells transduced with HSV not carrying the ICAM gene. Tumorigenicity of HSV-hICAM1-transduced tumor cells were tested in syngeneic Buffalo rats. Additionally, immunization with irradiated (10,000 rads) HSV-hICAM1-transduced tumor cells was performed to determine its effect on tumor growth. A 20-min exposure of tumor cells at a multiplicity of infection (MOI) of 1 resulted in high-level cell surface expression of human ICAM in approximately 25% of tumor cells. Transduced rat or human tumor cells exhibited significantly enhanced binding of lymphocytes (p < 0.05). HSV-hICAM1-transduced cells elicited an increase in infiltration by CD4+ lymphocytes in vivo and exhibited decreased tumorigenicity. Immunization with irradiated HSV-hICAM1-transduced cells protected against growth of subsequent injected parental tumor cells. HSV amplicon-mediated gene transfer is an efficient method for modifying the cell surface expression of adhesion molecules. Increased tumor expression of ICAM-1 represents a promising immune anti-cancer strategy.
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Citations
•Journal Article
Gene therapy for cancer: What have we done and where are we going?
TL;DR: A review of clinical trial results to date indicates that these treatments can mediate tumor regression with acceptably low toxicity and important areas for future research include modifying viral vectors to reduce toxicity and immunogenicity, and increasing the transduction efficiency of nonviral vectors.
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Use of an oncolytic virus secreting GM-CSF as combined oncolytic and immunotherapy for treatment of colorectal and hepatic adenocarcinomas.
Sandeep Malhotra,Teresa Kim,Jonathan S. Zager,Joseph J. Bennett,Michael I. Ebright,Michael I. D’Angelica,Yuman Fong +6 more
TL;DR: Viral vectors combining oncolytic and immunotherapy are promising agents in treatment of colorectal carcinoma and hepatoma and there was no difference in the antitumor efficacy of these viruses in mice depleted of CD4+ and CD8+ T lymphocytes.
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Reduced expression of intercellular adhesion molecule-1 in ovarian adenocarcinomas.
Jeremy Arnold,Margaret C. Cummings,David M. Purdie,Georgia Chenevix-Trench,Georgia Chenevix-Trench +4 more
TL;DR: Investigation of gene expression in ovarian adenocarcinoma using a cDNA array containing 588 known human genes found that intercellular adhesion molecule-1 (ICAM-1) was expressed at lower levels in the ovarian tumour cell lines OAW42, PEO1 and JAM than in the immortalised human ovarian surface epithelial cell line HOSE 17.1.
Molecular targeting of antiangiogenic factor 16K hPRL inhibits oxygen-induced retinopathy in mice.
Hao Pan,Ngoc Quynh Nhu Nguyen,Hiroshi Yoshida,Frauke Bentzien,Lynn C. Shaw,Françoise Rentier-Delrue,Joseph Martial,Richard I. Weiner,Ingrid Struman,Maria B. Grant +9 more
TL;DR: A potential therapeutic role for 16K hPRL in the treatment of proliferative retinopathies is suggested, as it was expressed in virus-infected ABAE cells and resulted in a dose-dependent inhibition of cell proliferation.
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Dendritic Cells Transduced with HSV-1 Amplicons Expressing Prostate-Specific Antigen Generate Antitumor Immunity in Mice
Richard A. Willis,William J. Bowers,Michael J. Turner,Terrence L. Fisher,C. Siddiq Abdul-Alim,Darlene F. Howard,Howard J. Federoff,Edith M. Lord,John G. Frelinger +8 more
TL;DR: Results indicate that DCs transduced with HSV-1 amplicon vectors may provide a tool for investigation of the biology of CTL activation by DCs and a new modality for immunotherapy of cancer.
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