Intravesical BCG is a highly effective treatment for high-grade nonmuscle invasive bladder cancer and carcinoma in situ (CIS); however, for patients who are either resistant or become unresponsive to BCG therapy there is a need for alternative treatment approaches. This study examined the safety and feasibility of intravesically administered recombinant fowlpox virus encoding GM-CSF (Arm A) or TRICOM (Arm B); and the local and systemic immunologic responses generated to the vector(s). Twenty bladder cancer patients scheduled for cystectomy as their standard of care received preoperatively four weekly doses of intravesical recombinant fowlpox. Treatment was well tolerated, however, three patients experienced transient elevations of liver transaminases, with one rising to the level of a DLT. Cystectomy derived tumor and normal bladder mucosa demonstrated mRNA for the virally encoded LacZ gene supporting effective infection/transfection. Detected serum antibody to the LacZ encoding β-galactosidase indicated successful expression of vector-encoding gene products and the ability to immunize via the bladder site. H&E and IHC using a panel of immune cell specific antigens demonstrated immune cell infiltration of the bladder wall. These findings demonstrate good safety profile, successful infection/transfection, ability to generate systemic immune response, and local recruitment of immune cell populations with intravesical administration of fowlpox-based constructs encoding for GM-CSF(rF-GM-CSF) or TRICOM (rF-TRICOM), and support further evaluation of this treatment modality for bladder cancer.

Cancer gene therapy. 2019 Jun 20 [Epub ahead of print]

Daniella E Portal, Robert E Weiss, Malgorzata Wojtowicz, Amal Mansour, Claude Monken, Janice M Mehnert, Joseph A Aisner, Michael Kane, Jennifer Nishioka, Seena Aisner, Stephen Peters, Mark N Stein, Isaac Y Kim, Tina M Mayer, Weichung Shih, James Gulley, Howard Streicher, Eric A Singer, Edmund C Lattime

Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, 195 Little Albany Street, New Brunswick, NJ, USA., Department of Pathology and Laboratory Medicine, Rutgers New Jersey Medical School, Newark, NJ, USA., Section of Urologic Oncology, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, USA., Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA., Investigational Drug Branch, National Institutes of Health, Bethesda, MD, USA., Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, 195 Little Albany Street, New Brunswick, NJ, USA. .