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.

Keywords: Bacillus Calmette-Guérin (BCG); Bladder cancer; Immune response; Intradermal; Safety.

© 2025 The Authors.

目标： 确定在系统性皮内卡介苗（BCG）预处理的情况下，皮内卡介苗对膀胱内卡介苗免疫反应的安全性和细胞因子及蛋白酶调节的作用。

方法： I期和机制纵向、前瞻性单盲随机研究（NCT04806178）。2021年9月至2023年4月期间，在一家教学医院接受经尿道膀胱肿瘤切除术后膀胱内辅助卡介苗治疗的非肌层浸润性尿路上皮膀胱癌患者共21例被随机分配到0.1毫升皮内卡介苗疫苗或安慰剂（0.9%生理盐水）组，注射时间在开始膀胱内卡介苗治疗前15天。从血液样本中机械评估了八种细胞因子的血清水平：干扰素诱导跨膜蛋白3基因（IFITM3）、白细胞介素-1β（IL1-BETA）、白细胞介素-2受体α链（IL2 RA）、白细胞介素-6（IL 6）、白细胞介素-10（IL 10）、肿瘤坏死因子-α（TNF-α）、干扰素-β、AXL以及一种蛋白酶CASPASE 8。

结果： 排除一名患者后，共有20名患者被随机分配到皮内卡介苗组(n = 11)和皮内安慰剂组(n = 9)。在接受膀胱内Onco-BCG治疗过程中没有观察到不良反应的差异，并且在对照组与干预组之间以及随时间变化分析的目标细胞因子及蛋白酶表达水平上也没有发现差异。

结论： 在进行膀胱内应用之前给予皮内卡介苗是安全的，不会增加不良反应。此外，在膀胱内诱导期BCG治疗期间，它似乎也不会改变所分析的目标。未来应探索其他免疫靶标。由于在巴西结核病流行地区，卡介苗接种是强制性的，这可能影响了研究结果。

关键词： 卡介苗（BCG）；膀胱癌；免疫反应；皮内给药；安全性。

© 2025 The Authors.