Abstract 2657: Immune checkpoint therapy as a treatment option for non-muscle invasive bladder cancer

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 (6Suppl): Abstract nr 2657.