(UroToday.com) The 2026 American Urological Association annual meeting featured a non-invasive bladder cancer session and a presentation by Dr. Taylor Goodstein discussing immune microenvironment signatures of response to cretostimogene grenadenorepvec in BCG-unresponsive non-muscle invasive bladder cancer.
Cretostimogene grenadenorepvec is a novel agent under investigation for BCG-unresponsive non-muscle invasive bladder cancer, an adenoviral dual-mechanistic oncolytic gene therapy. The BOND-003 phase 3 clinical trial demonstrated a 75% complete response rate at any time with cretostimogene. Dr. Goodstein and colleagues investigated a cohort of cretostimogene-treated patients with variable responses for whom tissue is available to perform multiplex immunofluorescence, to better understand the tumor microenvironment associated with treatment response.
Patients who received cretostimogene for whom at least one pre- and one post-treatment FFPE tissue sample were available were included. Multiplex immunofluorescence staining was performed with the Opal Polaris 7-color fluorescence immunohistochemistry kit. Antibodies used were CD8, FoxP3, TCF1, PD1, MHC-II, and CD4. Vectra Polaris Automated Quantitative Pathology Imaging System was used for multispectral imaging. QuPath-0.2.3 was used to quantify whole slide fluorescence intensity within each cell and calculate cellular density. Patients were classified as a responder if they had no recurrence during follow-up, early non-responder if they developed high-grade recurrence < 1 year after starting cretostimogene, late non-responder if they recurred > 1 year after starting treatment, and progressors if they were upstaged to > T1 at any point during follow-up.
A total of 15 specimens from six patients were included (1 responder, 3 early non-responders, 1 late non-responder, and 1 progressor). There was no difference in post-treatment recruitment of CD8+ or CD4+ cells between responders (responder + late non-responder) versus non-responders (early non-responder + progressor). An increased post-treatment ratio of CD8+ to FOXP3+ cells was seen with responders compared to non-responders:
An increased ratio of CD4+/FOXP3+ and CD4+/PD1+ was also seen with responders compared to non-responders. The following figure highlights mature tertiary lymphoid structure in a responder patient after induction of cretostimogene. Following reinduction, the patient has been recurrence-free for over 24 months. Additional early tertiary lymphoid structures/lymphoid aggregates can be seen elsewhere in the tissue specimen, identified with white arrowheads:
Dr. Goodstein concluded her presentation discussing immune microenvironment signatures of response to cretostimogene grenadenorepvec in BCG-unresponsive non–muscle invasive bladder cancer with the following take-home points:
- In this analysis of multiplex immunofluorescence performed in patients who received cretostimogene, pre- and post-treated tissue demonstrates immunologic hallmarks of response versus non-response that are similar to what has been shown in other studies in bladder cancer
- These data indicate that effective anti-tumor immunity in this context depends less on total immune infiltration and more on the equilibrium between effector and regulatory immune subsets
Presented by: Taylor Goodstein, MD, Urologic Oncology Fellow, Emory University, Atlanta, GA
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the American Urological Association (AUA) 2026 Annual Meeting, Washington, DC, Fri, May 15 – Mon, May 18, 2026.