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
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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.
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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.
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Dendritic Cells Transduced with HSV-1 Amplicons Expressing Prostate-Specific Antigen Generate Antitumor Immunity in Mice
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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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References
Downregulation of cell adhesion molecules LFA-3 and ICAM-1 in Epstein-Barr virus-positive Burkitt's lymphoma underlies tumor cell escape from virus-specific T cell surveillance.
TL;DR: It is postulated that downregulation of the adhesion molecules LFA-3 and ICAM-1 on EBV+ BL underlies the ability of the malignant clone to evade EBV-specific T cell surveillance in vivo.
347
Functional evidence that intercellular adhesion molecule-1 (ICAM-1) is a ligand for LFA-1-dependent adhesion in T cell-mediated cytotoxicity.
M. W. Makgoba,Martin E. Sanders,G. E. Ginther Luce,E A Gugel,Michael L. Dustin,Timothy A. Springer,Stephen Shaw +6 more
TL;DR: The present studies investigate the importance of ICAM‐1 for human cytotoxic T lymphocytes (CTL), both in their formation of antigen‐independent conjugates (AIC) and in their lysis of targets.
346
Constitutive expression of B7 restores immunogenicity of tumor cells expressing truncated major histocompatibility complex class II molecules
Sivasubramanian Baskar,Suzanne Ostrand-Rosenberg,Nasrin Nabavi,Lee M. Nadler,Gordon J. Freeman,Laurie H. Glimcher +5 more
TL;DR: The role of B7 activation molecule is illustrated in stimulating potent tumor-specific CD4+ T cells that mediate rejection of wild-type tumors and provides a theoretical basis for immunotherapy of established tumors.
311
•Journal Article
Shedding of ICAM-1 from human melanoma cell lines induced by IFN-gamma and tumor necrosis factor-alpha. Functional consequences on cell-mediated cytotoxicity.
TL;DR: Sliding of ICAM-1 may be one of the mechanisms by which neoplastic cells escape immunosurveillance and the non-MHC-restricted cytotoxicity mediated by NK and lymphokine-activated killer cells could be abrogated either by purified soluble IC AM-1 or by melanoma cell culture supernatants containing shed ICam-1.
292
•Journal Article
Interleukin 6 Gene Transfection into Lewis Lung Carcinoma Tumor Cells Suppresses the Malignant Phenotype and Confers Immunotherapeutic Competence against Parental Metastatic Cells
Angel Porgador,Esther Tzehoval,Anne Katz,Ezra Vadai,Michel Revel,Michael Feldman,Lea Eisenbach +6 more
TL;DR: Inactivated IL-6 transfectants were effective when used as a cellular vaccine for experimental immunotherapy of metastasis and prevented metastatic growth of parental highly metastatic D122 cells when immunization of mice was begun after establishment of the primary parental tumors.
271