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John C. Bell, PhD
jbell@ohri.ca
Senior Scientist, Cancer Therapeutics, Ottawa Hospital Research Institute
Professor, Depts. of Medicine and Biochemistry, Microbiology & Immunology University of OttawaKey Words: oncolytic virus, protein translation, cancer, therapeutics
Research Interests
Oncolytic Viruses: Novel Cancer Therapeutics
Current cancer therapies for metastatic disease have limited efficacy and high toxicity and thus novel approaches to treatment are sought. Viruses have many characteristics which make them desirable as a therapeutic strategy for the treatment of cancer including their ability to infect cells and replicate, induce cell death, release viral particles and spread through human tissues. We have shown that a variety of viruses selectively replicate in and kill human cancer cell lines, primary patient samples and purge contaminated bone marrow of leukemic cells. Although the mechanisms of preferential oncolytic activity are incompletely understood, our hypothesis is that during tumor evolution, genetic abnormalities accumulate that, while providing malignancies a growth/survival advantage, also compromise the antiviral program of tumour cells. One cytokine pathway that seems to be frequently defective in tumour cell lines is the interferon signaling cascade. In particular, mutants of Rhabdovirus and Orthopoxviruses which strongly induce interferon expression are safe anti-cancer therapeutics in a variety of animal tumour models. We are optimizing and selecting for virus strains with improved efficacy. We are carrying out a detailed analysis of the behavior of tumour microenvironment cells during oncolytic virus therapy. In particular we have shown in both mouse models and samples taken from patients undergoing OV therapy that our viruses can infect and disrupt tumour vasculature. The affect of OV therapy on all aspects of tumour microenvironment (e.g. support cells, immune infiltrates) is under investigation.
Most Recent Publications (provided by The Ottawa Hospital Library Database)
Auer RA;Tai LH;Tanese de SC;Belanger S;Ly L;Alkayyal AA;Zhang J;Rintoul JL;Ananth AA;Lam T;Breitbach CJ;Falls TJ;Kirn DH;Bell JC;Makrigiannis AP;, (2013), Preventing post-operative metastatic disease by inhibiting surgery-induced dysfunction in natural killer cells, Cancer Res, Vol.73, Issue 1, 97-107 -> view abstractAuer RA;Tai LH;Tanese de SC;Belanger S;Ly L;Alkayyal AA;Zhang J;Rintoul JL;Ananth AA;Lam T;Breitbach CJ;Falls TJ;Kirn DH;Bell JC;Makrigiannis AP;, (2013), Preventing post-operative metastatic disease by inhibiting surgery-induced dysfunction in natural killer cells, Cancer Res, Vol.73, Issue 1, 97-107 -> view abstract
Seth R;Tai LH;Falls T;de Souza CT;Bell JC;Carrier M;Atkins H;Boushey R;Auer RA;, (2012 Oct 26), Surgical Stress Promotes the Development of Cancer Metastases by a Coagulation-Dependent Mechanism Involving Natural Killer Cells in a Murine Model, Ann Surg, -> view abstract
Bell JC;, (2012 Jun 13), The virus that came in from the cold, Sci Transl Med, Vol.4, Issue 138, 138fs17 -> view abstract
Lemay CG;Rintoul JL;Kus A;Paterson JM;Garcia V;Falls TJ;Ferreira L;Bridle BW;Conrad DP;Tang VA;Diallo JS;Arulanandam R;Le BF;Garson K;Vanderhyden BC;Stojdl DF;Lichty BD;Atkins HL;Parato KA;Bell JC;Auer RC;, (2012 Jul 3), Harnessing Oncolytic Virus-mediated Antitumor Immunity in an Infected Cell Vaccine, Mol Ther, Vol.20, Issue 9, 1791-1799 -> view abstract
Russell SJ;Peng KW;Bell JC;, (2012 Jul), Oncolytic virotherapy, Nat Biotechnol, Vol.30, Issue 7, 658-670 -> view abstract
Rintoul JL;Lemay CG;Tai LH;Stanford MM;Falls TJ;de Souza CT;Bridle BW;Daneshmand M;Ohashi PS;Wan Y;Lichty BD;Mercer AA;Auer RC;Atkins HL;Bell JC;, (2012 Jan 24), ORFV: A Novel Oncolytic and Immune Stimulating Parapoxvirus Therapeutic, Mol Ther, Vol.20, Issue 6, 1148-1157 -> view abstract
Auer R;Bell JC;, (2012 Jan), Oncolytic viruses: smart therapeutics for smart cancers, Future Oncol, Vol.8, Issue 1, 1-4
Le BF;Niknejad N;Wang J;Auer R;Weberpals JI;Bell JC;Dimitroulakos J;, (2012 Aug 1), Sensitivity of cervical carcinoma cells to vesicular stomatitis virus-induced oncolysis: Potential role of human papilloma virus infection, Int J Cancer, Vol.131, Issue 3, E204-E215 -> view abstract
Parato KA;Breitbach CJ;Le BF;Wang J;Storbeck C;Ilkow C;Diallo JS;Falls T;Burns J;Garcia V;Kanji F;Evgin L;Hu K;Paradis F;Knowles S;Hwang TH;Vanderhyden BC;Auer R;Kirn DH;Bell JC;, (2012 Apr), The Oncolytic Poxvirus JX-594 Selectively Replicates in and Destroys Cancer Cells Driven by Genetic Pathways Commonly Activated in Cancers, Mol Ther, Vol.20, Issue 4, 749-758 -> view abstract
Note: This is not a complete list of publications. More publications may be available in The Ottawa Hospital Library database and Pubmed (search by last name and initials).
