Abstract 2657: Immune checkpoint therapy as a treatment option for non-muscle invasive bladder cancer
Authors: Benmerzoug Sulayman , Louche Katie , Angles Thibault , Serhan Nizar , Dol-Gleizes Frederique , Lejeune Pascale , Chabot Sophie 
Published: March 2024

Abstract
Bladder cancer (BCa) is one of the most common malignancies with more than 500,000 new cases diagnosed each year. Intravesical instillations of Bacillus Calmette-Guérin (BCG) is the gold-standard treatment for non-muscle invasive BCa (NMIBC) patients despite significant side effects and high rates of refractory disease and/or recurrence. Indeed, treatment failure occurs in ~40% of cases emphasizing the urgent need to evaluate alternative and/or complementary new therapies including immunotherapies. Recently, the use of immune checkpoint inhibitor (ICI) anti-PD-1 therapy has been approved for the treatment of BCG-unresponsive NMIBC patients. Here, we investigated whether targeting PD-1 or CTLA-4 can boost anti-tumor immunity in the orthotopic murine MB49 BCa model. To this purpose, 2.5 × 105 luciferase-expressing MB49 cells (MB49-Luc) have been instilled into the preconditioned bladder of female C57Bl/6 mice by intra-urethral catheterization. In vivo tumor growth has been monitored three times a week using the IVIS spectrum in vivo imaging system. All the inoculated mice showed a luciferase signal at day 3 post-bladder tumor inoculation, demonstrating 100% of tumor uptake. Based on the in vivo bioluminescence, a randomization has been performed before ICI treatment consisting of anti-CTLA-4 (10 μg/mouse; q3dx4, intraperitoneal) or anti-PD-1 (100 μg/mouse, q3dx4, intraperitoneal). Our data indicate that ICI treatments significantly decreased the in vivo bioluminescence, indicating reduced tumor growth. Furthermore, anti-CTLA-4 and anti-PD-1 administration resulted in a significant long term anti-tumor activity, with ~90% and ~70% overall survival of anti-CTLA-4 and anti-PD-1 treated mice, respectively, while isotype control mice displayed ~10% survival by day 74 post-MB49-Luc cells inoculation. To investigate the potential development of systemic adaptive anti-tumor immunity elicited by ICI treatment, remaining ICI-treated mice and newly onboarded non-treated control mice have been (re)-challenged with MB49 tumor cells subcutaneously (s.c.). While all the control mice showed tumor outgrowth and needed to be sacrificed due to humane endpoint by the day 32 post-s.c. challenge, rechallenged ICI-treated mice showed potent abscopal effect and displayed no tumor engraftment with 100% overall survival. Altogether, these findings demonstrate that systemic ICI immunotherapies such as PD-1 and CTLA-4 elicit potent anti-tumor activity and induce protective anti-tumor immune memory. ICI might present an alternative or a complementary treatment to BCG therapy for NMIBC patients.
Citation Format: Sulayman Benmerzoug, Katie Louche, Thibault Angles, Nizar Serhan, Frederique Dol-Gleizes, Pascale Lejeune, Sophie Chabot. Immune checkpoint therapy as a treatment option for non-muscle invasive bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2657.