J Andrea McCart

J Andrea McCart, MSc, MD, FRCSC

Dr. McCart completed medical school and General Surgery training at the University of Western Ontario. During her residency, she undertook research studying p53 mutations in esophageal cancer and obtained her MSc in Pathology in 1995. Following residency, she completed a surgical oncology fellowship focused on regional therapies of cancer at the National Cancer Institute in Bethesda, Maryland. While there, she also did postdoctoral research in the laboratory of Dr. David Bartlett, investigating gene and viral therapies for cancer. Dr. McCart moved to Toronto in 2001, where she is currently an Assistant Professor in the Department of Surgery and a Scientist at the Toronto General Hospital Research Institute. Her clinical interests include treatment of peritoneal malignancies and gastrointestinal surgical oncology. Her research laboratory is developing novel viral-based therapeutics for peritoneal and other malignancies.
 
Oncolytic Virotherapy
Some of the same genetic defects that cause a normal cell to transform into a cancer cell also allow viruses to enter and replicate virtually unchecked, creating a natural therapeutic window between normal and tumour tissues that we can utilize to develop novel viral therapies for cancer.

Our laboratory focuses on using vaccinia virus to treat a wide variety of cancers, including metastatic colon or ovarian cancer, and other cancers of the peritoneal cavity (such as mesothelioma). Our research covers the spectrum of new bio-therapeutic development, from discovery to preclinical investigations in small animals to safety studies in large animals. Planning for a phase I clinical trial is underway.

Current laboratory projects

  • Combined oncolytic virotherapy and targeted radiotherapy for peritoneal carcinomatosis:
    This project, supported by the Canadian Institutes of Health Research, aims to investigate the potential of treating peritoneal carcinomatosis by combining a double-deleted oncolytic vaccinia virus (vvDD) encoding a receptor that can be specifically targeted by radiotherapeutic agents (111In- and 177Lu-labeled DOTATOC). The vvDD used in this project selectively infects, replicates in and kills cancer cells. Expression of the receptor also allows targeting with the radiotherapeutic agents that may enhance the cytotoxic effects against non-infected tumour cells and help address the challenge of elimination of the virus by the immune system.
     
  • Molecular Assay of Virotherapy for Colon Carcinomatosis:
    This project supported by Colon Cancer Canada seeks to develop an assay that helps identify early on whether or not a productive vaccinia infection is occurring in the colon cancer samples. This will ultimately lead to a more personalized approach to treating cancer with viruses.
     
  • Development of a novel virotherapy strategy to detect and treat malignant peritoneal mesothelioma:
    The goal of this study, which is supported by the Mesothelioma Applied Research Foundation Grant in Memory of Ken Bendix, is to show that a vaccinia virus expressing a fluorescent protein will infect and kill mesothelioma cells. We predict that this will aid in earlier diagnosis with the use of fluorescent imaging and that the virus will be able to kill residual tumour cells after surgical debulking of the main tumour. If successful, we aim to translate this treatment into patients as soon as possible.
     
  • Development of novel tumour-specific vaccinia viruses:
    The objectives of this project are to develop and evaluate new vaccinia viruses that will be more tumour-specific than the current generation of viruses. This will allow us to safely use higher viral doses, or deliver ''toxic'' genes directly to the tumour but not normal tissue.
     
Int J Colorectal Dis. 2017 Dec 28;:
Angarita FA, Feinberg AE, Feinberg SM, Riddell RH, McCart JA
Mol Ther Oncolytics. 2016;3:16027
Evgin L, Ilkow CS, Bourgeois-Daigneault MC, de Souza CT, Stubbert L, Huh MS, Jennings VA, Marguerie M, Acuna SA, Keller BA, Lefebvre C, Falls T, Le Boeuf F, Auer RA, Lambris JD, McCart JA, Stojdl DF, Bell JC
Mol Ther. 2016 May 16;
Downs-Canner S, Sheng Guo Z, Ravindranathan R, Breitbach CJ, O'Malley ME, Jones HL, Moon A, McCart JA, Shuai Y, Zeh HJ, Bartlett DL
Ann Surg Oncol. 2016 Apr 19;
Hamilton TD, Taylor EL, Cannell AJ, McCart JA, Govindarajan A
Cancer Cell. 2015 Jul 22;
Arulanandam R, Batenchuk C, Angarita FA, Ottolino-Perry K, Cousineau S, Mottashed A, Burgess E, Falls TJ, De Silva N, Tsang J, Howe GA, Bourgeois-Daigneault MC, Conrad DP, Daneshmand M, Breitbach CJ, Kirn DH, Raptis L, Sad S, Atkins H, Huh MS, Diallo...
Mol Oncol. 2015 May 6;
Ottolino-Perry K, Acuna SA, Angarita FA, Sellers C, Zerhouni S, Tang N, McCart JA
Mol Ther. 2015 Mar 25;
Evgin L, Acuna SA, Tanese de Souza C, Marguerie M, Lemay CG, Ilkow CS, Findlay CS, Falls T, Parato KA, Hanwell D, Goldstein A, Lopez R, Lafrance S, Breitbach CJ, Kirn D, Atkins H, Auer RC, Thurman JM, Stahl GL, Lambris JD, Bell JC, McCart JA
Mol Ther. 2014 Oct 8;
Zeh HJ, Downs-Canner S, McCart JA, Guo ZS, Rao UN, Ramalingam L, Thorne SH, Jones HL, Kalinski P, Wieckowski E, O'Malley ME, Daneshmand M, Hu K, Bell JC, Hwang TH, Moon A, Breitbach CJ, Kirn DH, Bartlett DL
Ann Surg Oncol. 2014 Jul;21(7):2259-66
Acuna SA, Ottolino-Perry K, Çako B, Tang N, Angarita FA, McCart JA

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Assistant Professor, Department of Surgery, University of Toronto