Bell Lab

Our research program is directed towards the identification and characterization of novel cancer killing therapeutic viruses that selectively infect and kill cancer cells, while leaving healthy cells and tissues unharmed. Not only do we discover and design new therapeutic viruses, but we also manufacture them for eventual clinical translation and commercialization.

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

Kwame Twumasi-Boateng, Jessica L. Pettigrew, Y. Y. Eunice Kwok, John C. Bell & Brad H. Nelson. Oncolytic viruses as engineering platforms for combination immunotherapy. Nature Reviews Cancer. Published online: 25 April 2018. doi:10.1038/s41568-018-0009-4. Free full text. 

Bourgeois-Daigneault MC, Roy DG, Aitken AS, El Sayes N, Martin NT, Varette O, Falls T, St-Germain LE, Pelin A, Lichty BD, Stojdl DF, Ungerechts G, Diallo JS and Bell JC. Neoadjuvant oncolytic virotherapy before surgery sensitizes triple-negative breast cancer to immune checkpoint therapy. Sci Transl Med. 2018 Jan 3;10(422). Free full text. 

Rozanne Arulanandam, Cory Batenchuk, Fernando A. Angarita, Kathryn Ottolino-Perry, Sophie Cousineau, Amelia Mottashed, Emma Burgess, Theresa J. Falls, Naomi De Silva, Jovian Tsang, Grant A. Howe, Marie-Claude Bourgeois-Daigneault, David P. Conrad, Manijeh Daneshmand, Caroline J. Breitbach, David H. Kirn, Leda Raptis, Subash Sad, Harold Atkins, Michael S. Huh, Jean-Simon Diallo, Brian Lichty, Carolina S. Ilkow, Fabrice Le Boeuf, Christina L. Addison, J. Andrea Mc Cart and John C. Bell. VEGF-mediated induction of PRD1-BF1/Blimp1 expression sensitizes tumour vasculature to oncolytic virus infection. Cancer Cell. 2015 Aug 10;28(2):210-24. 

Carolina S. Ilkow, Monique Marguerie, Cory Batenchuk, Justin Mayer, Daniela Ben Neriah, Sophie Cousineau, Theresa Falls, Victoria Jennings, Meaghan Boileau, David Bellamy1, Donald Bastin1, Christiano Tanese de Souza1, Almohanad Alkayyal1, Jiging Zhang, Fabrice LeBoeuf1, Rozanne Arulanandam, Lawton Stubbert, Padma Sampath, Steve Thorne4, Piriya Paramanthan5, Avijit Chatterjee5, Robert M. Strieter, Marie Burdick, Christina Addison David F. Stojdl, Harold L. Atkins, Rebecca Auer, , Jean-Simon Diallo, Brian Lichty, and John C. Bell. Reciprocal cellular cross-talk within the tumor microenvironment promotes oncolytic virus activity. Nat Med. 2015 May;21(5):530-6.

Brian D. Lichty, Caroline J. Breitbach, David F. Stojdl, & John C. Bell. Going viral with cancer immunotherapy. Nature Reviews Cancer. 2014 03 July.

Fabrice Le Bœuf*, Cory Batenchuk*, Markus Vähä-Koskela, Sophie Breton, Dominic Roy, Chantal Lemay, Julie Cox, Hesham Abdelbary, Theresa Falls, Girija Waghray, Harold Atkins, David Stojdl, Jean-Simon Diallo, Mads Kaern, John Bell. Model-based Rational Design of an Oncolytic Virus with Improved Therapeutics Potential. Nature Communications 2013 Jun 14;4:1974. 

Heo, J.,Reid, T., Ruo, L., Breitbach, C.,Rose, S., Bloomston, M., Cho, M., Lim, H.Y., Chung, H.C., Kim, C.W., Burke, J.,Lencioni, R., Hickman, T., Moon, A., Lee, Y.S., Kim, M.K., Daneshmand, M., Dubois, K., Longpre, L., Ngo, M., Rooney, C., Bell, J.C.,Rhee,B-G., Patt, R., Hwang, T-H., Kirn, D.H., (2013) Randomized dose-finding clinical trial of oncolytic immunotherapeutic vaccinia JX 594 in liver cancer. Nat Med. 2013 Mar;19(3):329-36.