癌症免疫治疗已迅速成为继手术、放疗、化疗之后的第四种主流治疗选择，并取得了一些可喜的结果。它的目的是通过动员或刺激细胞毒性免疫细胞来杀死肿瘤细胞。然而，由于缺乏足够的递送途径和高毒性，肿瘤免疫疗法的临床应用受到限制。最近，纳米材料和基因工程通过保护抗原的传递、激活靶向T细胞、调节免疫抑制肿瘤微环境和提高治疗效果，在克服这些局限性方面显示出巨大的潜力。卡介苗（BCG）是一种用于预防结核病的牛分枝杆菌减毒活疫苗，于1927年首次报道其具有抗肿瘤活性。卡介苗疗法可通过诱导多种细胞因子和趋化因子来激活免疫系统，其特异性免疫和炎症反应发挥抗肿瘤作用。卡介苗于20世纪70年代首次作为膀胱癌膀胱灌注治疗剂使用，有效提高免疫抗肿瘤活性，预防肿瘤复发。最近，纳米卡介苗和基因工程卡介苗被提议作为膀胱癌的治疗替代方案，因为它们能够诱导更强、更稳定的免疫反应。在这项研究中，我们概述了用于膀胱癌免疫治疗的纳米卡介苗和基因工程卡介苗的开发，并回顾了它们的潜力和相关挑战。

Cancer immunotherapy has rapidly become the fourth mainstream treatment alternative after surgery, radiotherapy, and chemotherapy, with some promising results. It aims to kill tumor cells by mobilizing or stimulating cytotoxic immune cells. However, the clinical applications of tumor immunotherapies are limited owing to a lack of adequate delivery pathways and high toxicity. Recently, nanomaterials and genetic engineering have shown great potential in overcoming these limitations by protecting the delivery of antigens, activating targeted T cells, modulating the immunosuppressive tumor microenvironment, and improving the treatment efficacy. Bacillus Calmette-Guérin (BCG) is a live attenuated Mycobacterium bovis vaccine used to prevent tuberculosis, which was first reported to have antitumor activity in 1927. BCG therapy can activate the immune system by inducing various cytokines and chemokines, and its specific immune and inflammatory responses exert antitumor effects. BCG was first used during the 1970s as an intravesical treatment agent for bladder cancer, which effectively improved immune antitumor activity and prevented tumor recurrence. More recently, nano-BCG and genetically engineered BCG have been proposed as treatment alternatives for bladder cancer due to their ability to induce stronger and more stable immune responses. In this study, we outline the development of nano-BCG and genetically engineered BCG for bladder cancer immunotherapy and review their potential and associated challenges.