Abstract 952: Intravesical instillation of a TME engineering viral vector increases survival in an orthotropic bladder cancer model

Abstract Gene engineering of the tumor microenvironment (TME) with viral vectors encoding immunostimulatory genes can inflame the TME and create the basis for an immune response against the tumor cells. Adm703 is an adenoviral vector based on the AdEasy system. Adm703 encodes for two murine immunostimulatory genes, trimerized membrane-bound CD40L and 4-1BBL that are expressed by all infected cells (tumor and stroma). The transgenes can induce maturation of dendritic cells and expansion and memory formation of T cells as well as shift the general pro-tumorigenic environment towards anti-tumor state by influencing both tumor and stroma cells. Non-muscle invasive urinary bladder cancer is currently treated with bacillus Calmette-Guérin (BCG) instillations followed by nadofaragene firadenovec-vncg for BCG refractory patients. If the tumor becomes muscle invasive, the patients are subjected to radical cystectomy in which the urinary bladder is removed. This surgery is severely disabling and there is an urgent need to develop a treatment that will lead to a long lasting immune control with a possibility to delay or avoid surgery. We hypothesize that LOAd703, the human equivalent to Adm703, may be an interesting option for these patients. An orthotopic bladder cancer mouse model was treated intravesically with Adm703 to evaluate if Adm703 can control tumor growth. Bladders of female C57Bl/6 mice were incubated with poly-L-lysin to enhance tumor uptake before implantation of MB49 cells. The mice received four intravesical treatments with Adm703 or sodium chlorine (control) on day 1, 8, 15, 22 after tumor instillation. Mice were monitored for hematuria which is an early sign of tumor take. If more than 10 percent weight loss occurred the mice were sacrificed. The mice treated with Adm703 had less hematuria during treatment and had increased survival (mOS=40 days) compared to the control group (mOS=12 days). In conclusion, TME gene engineering with TMZ-CD40L and 4-1BBL increased survival of mice with orthotopic bladder cancer. Further studies investigating Adm703's effect on the immune system are planned. Citation Format: Emma Eriksson, Ioannis Nikoloudis, Mariela Mejia Cordova, Tanja Lövgren, Angelica Loskog. Intravesical instillation of a TME engineering viral vector increases survival in an orthotropic bladder cancer model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 952.