For Patients: Information about participating in oncolytic virus clinical trials is available here.

Pour les patients : Renseignements sur la participation à des essais cliniques sur la virothérapie oncolytique

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 Ottawa

Key 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)

Cronin M;Le BF;Murphy C;Roy DG;Falls T;Bell JC;Tangney M;, (2014 Feb 26), Bacterial-mediated knockdown of tumour resistance to an oncolytic virus enhances therapy, Mol Ther, -> view abstract

Beug ST;Tang VA;Lacasse EC;Cheung HH;Beauregard CE;Brun J;Nuyens JP;Earl N;St-Jean M;Holbrook J;Dastidar H;Mahoney DJ;Ilkow C;Le BF;Bell JC;Korneluk RG;, (2014 Feb), Smac mimetics and innate immune stimuli synergize to promote tumor death, Nat Biotechnol, Vol.32, Issue 2, 182-190 -> view abstract

Tai LH;Zhang J;Scott KJ;de Souza CT;Alkayyal AA;Ananth AA;Sahi S;Adair RA;Mahmoud AB;Sad S;Bell JC;Makrigiannis AP;Melcher AA;Auer RC;, (2013 Sep 15), Perioperative influenza vaccination reduces postoperative metastatic disease by reversing surgery-induced dysfunction in natural killer cells, Clin Cancer Res, Vol.19, Issue 18, 5104-5115 -> view abstract

Conrad DP;Tsang JJ;Maclean M;Diallo JS;Le BF;Lemay CG;Falls TJ;Parato K;Bell JC;Atkins H;, (2013 May 28), Leukemia Cell-Rhabdovirus Vaccine: Personalized Immunotherapy for Acute Lymphocytic Leukemia, Clin Cancer Res, Vol.19, Issue 14, 3832-3843 -> view abstract

Kim MK;Breitbach CJ;Moon A;Heo J;Lee YK;Cho M;Lee JW;Kim SG;Kang DH;Bell JC;Park BH;Kirn DH;Hwang TH;, (2013 May 15), Oncolytic and immunotherapeutic vaccinia induces antibody-mediated complement-dependent cancer cell lysis in humans, Sci Transl Med, Vol.5, Issue 185, 185ra63 -> view abstract

Heo J;Reid T;Ruo L;Breitbach CJ;Rose S;Bloomston M;Cho M;Lim HY;Chung HC;Kim CW;Burke J;Lencioni R;Hickman T;Moon A;Lee YS;Kim MK;Daneshmand M;Dubois K;Longpre L;Ngo M;Rooney C;Bell JC;Rhee BG;Patt R;Hwang TH;Kirn DH;, (2013 Mar), Randomized dose-finding clinical trial of oncolytic immunotherapeutic vaccinia JX-594 in liver cancer, Nat Med , Vol.19, Issue 3, 329-336 -> view abstract

Vaha-Koskela MJ;Le BF;Lemay C;De SN;Diallo JS;Cox J;Becker M;Choi Y;Ananth A;Sellers C;Breton S;Roy D;Falls T;Brun J;Hemminki A;Hinkkanen A;Bell JC;, (2013 Feb), Resistance to two heterologous neurotropic oncolytic viruses, Semliki Forest virus and vaccinia virus, in experimental glioma10, J Virol, Vol.87, Issue 4, 2363-2366 -> view abstract

Moussavi M;Tearle H;Fazli L;Bell JC;Jia W;Rennie PS;, (2013 Apr), Targeting and killing of metastatic cells in the transgenic adenocarcinoma of mouse prostate model with vesicular stomatitis virus, Mol Ther, Vol.21, Issue 4, 842-848 -> view abstract

Bridle BW;Chen L;Lemay CG;Diallo JS;Pol J;Nguyen A;Capretta A;He R;Bramson JL;Bell JC;Lichty BD;Wan Y;, (2013 Apr), HDAC inhibition suppresses primary immune responses, enhances secondary immune responses, and abrogates autoimmunity during tumor immunotherapy, Mol Ther, Vol.21, Issue 4, 887-894 -> view abstract

Seth R;Tai LH;Falls T;de Souza CT;Bell JC;Carrier M;Atkins H;Boushey R;Auer RA;, (2013), Surgical Stress Promotes the Development of Cancer Metastases by a Coagulation-Dependent Mechanism Involving Natural Killer Cells in a Murine Model, Ann Surg, Vol.258, Issue 1, 158-168 -> 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).