Open Access

ARTICLE

Intradermal priming to intravesical Bacillus Calmette-Guérin in non-muscle invasive bladder cancer: A translational research and phase I clinical trial

LUCIANA SABOYA^1,2, KEINI BUOSI¹, TIAGO SILVA², ELAINE CANDIDO¹, JOSIANE MORARI³, LICIO A. VELLOSO³, SHAHROKH F. SHARIAT^4,5,6,7, MARCUS V. SADI², LEONARDO O. REIS^1,8,9,*

1 UroScience, School of Medical Sciences, University of Campinas, Campinas, 13083-887, Brazil
2 Department of Urology, Federal University of São Paulo, EPM, São Paulo, 04023-062, Brazil
3 Obesity and Comorbidities Research Center, University of Campinas, Campinas, 13083-887, Brazil
4 Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, 1090, Austria
5 Hourani Center for Applied Scientific Research, Al-Ahliyya Amman University, Amman, 19328, Jordan
6 Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
7 Department of Urology, Weill Cornell Medical College, New York, NY 10065, USA
8 ImmunOncology, Pontifical Catholic University of Campinas, Campinas, São Paulo, 13060-904, Brazil
9 UroGen, National Institute of Science, Technology and Innovation in Genitourinary Cancer (INCT), Campinas, São Paulo, 13087-571, Brazil

* Corresponding Author: LEONARDO O. REIS. Email:

(This article belongs to the Special Issue: Advances in Genitourinary Cancer)

Oncology Research 2025, 33(6), 1495-1503. https://doi.org/10.32604/or.2025.061812

Received 03 December 2024; Accepted 01 April 2025; Issue published 29 May 2025

Abstract

Objective: To determine the safety and the role of modulating cytokines and proteases in the immune response to intravesical Bacillus Calmette-Guérin (BCG) when primed with systemic intradermal BCG. Methods: Phase 1 and mechanistic longitudinal, prospective, single-blind randomized study (NCT04806178). Twenty-one non-muscle invasive urothelial bladder cancer patients undergoing intravesical adjuvant BCG after transurethral resection of bladder tumor (TURBT) in a teaching hospital between September 2021 and April 2023 were randomized to 0.1 mL of intradermal BCG vaccine or placebo (0.9% saline) administered 15 days before the start of intravesical BCG therapy. Blood samples were evaluated mechanistically regarding eight cytokines serum levels interferon-induced transmembrane protein 3 Gene (IFITM3), Interleukin 1 beta (IL1-BETA), interleukin-2 receptor alpha chain (IL2 RA), Interleukin 6 (IL 6), Interleukin 10 (IL 10), Tumor necrosis factor alpha (TNF-α), Interferon-β, AXL, and one protease CASPASE 8. Results: After 1 exclusion, twenty patients were randomized to intradermal BCG (n = 11) and intradermal placebo (n = 9). There was no difference in adverse effects emerging from the intravesical Onco-BCG therapy, and no difference in the expression of the cytokines and proteases analyzed between control and intervention, and over time. Conclusions: Intradermal BCG administration before intravesical application was safe, with no increase in adverse effects. It also does not seem to change the analyzed targets during the intravesical induction-phase BCG. Other immune targets should be explored in the future. The Brazilian tuberculosis-endemic status, where BCG vaccination is mandatory, might have affected the results.

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