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 ORCID:

Sheng ZENG

0000-0002-6795-8024

Yifei ZHANG

0000-0001-5961-9180

Haifeng WANG

0009-0008-4653-2316

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Journal of Zhejiang University SCIENCE B 2024 Vol.25 No.7 P.557-567

http://doi.org/10.1631/jzus.B2300392


Nano-Bacillus Calmette-Guérin immunotherapies for improved bladder cancer treatment


Author(s):  Sheng ZENG, Shaoqiang XING, Yifei ZHANG, Haifeng WANG, Qian LIU

Affiliation(s):  Department of Urology, Tianjin First Central Hospital, Tianjin 300192, China; more

Corresponding email(s):   whfhf@sina.com, simonlq@163.com

Key Words:  Bladder cancer, Bacillus Calmette-Gué, rin vaccine, Nanocarrier, Genetic engineering, Immunotherapy


Sheng ZENG, Shaoqiang XING, Yifei ZHANG, Haifeng WANG, Qian LIU. Nano-Bacillus Calmette-Guérin immunotherapies for improved bladder cancer treatment[J]. Journal of Zhejiang University Science B, 2024, 25(7): 557-567.

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Abstract: 
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-Gué;rin (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.

纳米卡介苗改善膀胱癌的免疫治疗效果

曾胜1,邢绍强2,张毅飞2,王海峰1,刘谦1
1天津市第一中心医院泌尿外科,中国天津市,300192
2天津医科大学第一中心临床学院泌尿外科,中国天津市,300192
摘要:癌症免疫治疗已成为继手术、放疗和化疗之后的第四大主流治疗选择,并取得了令人鼓舞的成果。肿瘤免疫治疗通过调动或激发机体自身的免疫功能,从而抑制和杀伤肿瘤细胞。然而,肿瘤免疫治疗作为一种新兴的治疗手段,由于缺乏有效的免疫细胞传递途径以及具有较高的毒副作用,在临床上的应用受到限制。近年来,纳米材料和基因工程在保护抗原递送、激活靶向T细胞、调节免疫抑制的肿瘤微环境和提高治疗效果等方面显示出巨大的潜力。卡介苗是一种用于预防结核病的减毒牛分枝杆菌活疫苗,于1927年首次报道其抗肿瘤活性。卡介苗可通过诱导多种细胞因子和趋化因子激活免疫系统,其特异性免疫和炎症反应可发挥抗肿瘤作用。20世纪70年代,卡介苗首次作为治疗膀胱癌的膀胱灌注药物,有效地提高了免疫抗肿瘤活性,防止肿瘤复发。最近,纳米卡介苗和基因工程卡介苗因其能诱导更强且更稳定的免疫反应,被提出作为膀胱癌的治疗方案。在本研究中,我们概述了纳米卡介苗和基因工程卡介苗用于膀胱癌免疫治疗的发展,并回顾了它们的潜力和挑战。

关键词:膀胱癌;卡介苗;纳米载体;基因工程;免疫治疗

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]AkazawaT, MasudaH, SaekiY, et al., 2004. Adjuvant-mediated tumor regression and tumor-specific cytotoxic response are impaired in MyD88-deficient mice. Cancer Res, 64(2):757-764.

[2]Álvarez-MaestroM, Guerrero-RamosF, Rodríguez-FabaO, et al., 2021. Current treatments for BCG failure in non-muscle invasive bladder cancer (NMIBC). Actas Urol Esp, 45(2):93-102.

[3]AndersenCS, DietrichJ, AggerEM, et al., 2007. The combined CTA1-DD/ISCOMs vector is an effective intranasal adjuvant for boosting prior Mycobacterium bovis BCG immunity to Mycobacterium tuberculosis. Infect Immun, 75(1):408-416.

[4]AzumaI, SeyaT, 2001. Development of immunoadjuvants for immunotherapy of cancer. Int Immunopharmacol, 1(7):1249-1259.

[5]BabjukM, BurgerM, CapounO, et al., 2022. European Association of Urology guidelines on non-muscle-invasive bladder cancer (Ta, T1, and carcinoma in situ). Eur Urol, 81(1):75-94.

[6]BeversRFM, KurthKH, SchamhartDHJ, 2004. Role of urothelial cells in BCG immunotherapy for superficial bladder cancer. Br J Cancer, 91(4):607-612.

[7]BhindiB, KoolR, KulkarniGS, et al., 2021. Canadian Urological Association guideline on the management of non-muscle-invasive bladder cancer – Abridged version. Can Urol Assoc J, 15(8):230-239.

[8]BöhleA, BrandauS, 2003. Immune mechanisms in bacillus Calmette-Guerin immunotherapy for superficial bladder cancer. J Urol, 170(3):964-969.

[9]BrandauS, SuttmannH, 2007. Thirty years of BCG immunotherapy for non-muscle invasive bladder cancer: a success story with room for improvement. Biomed Pharmacother, 61(6):299-305.

[10]BurgerM, CattoJWF, DalbagniG, et al., 2013. Epidemiology and risk factors of urothelial bladder cancer. Eur Urol, 63(2):234-241.

[11]BussJH, BegniniKR, BenderCB, et al., 2018. Nano-BCG: a promising delivery system for treatment of human bladder cancer. Front Pharmacol, 8:977.

[12]ChoMJ, KimMJ, KimK, et al., 2019. The immunotherapeutic effects of recombinant Bacillus Calmette-Guérin resistant to antimicrobial peptides on bladder cancer cells. Biochem Biophys Res Commun, 509(1):167-174.

[13]ChoiSY, KimSJ, ChiBH, et al., 2015. Modulating the internalization of bacille Calmette-Guérin by cathelicidin in bladder cancer cells. Urology, 85(4):964.e7-964.e12.

[14]ChouR, SelphS, BuckleyDI, et al., 2017. Intravesical therapy for the treatment of nonmuscle invasive bladder cancer: a systematic review and meta-analysis. J Urol, 197(5):1189-1199.

[15]ErdoğarN, IskitAB, EroğluH, et al., 2015. Antitumor efficacy of bacillus Calmette-Guerin loaded cationic nanoparticles for intravesical immunotherapy of bladder tumor induced rat model. J Nanosci Nanotechnol, 15(12):‍‍10156-10164.

[16]FleischmannJD, ParkMC, HassanMO, 1993. Fibronectin expression on surgical specimens correlated with the response to intravesical bacillus Calmette-Guerin therapy. J Urol, 149(2):268-271.

[17]GadiotJ, HooijkaasAI, KaiserADM, et al., 2011. Overall survival and PD-L1 expression in metastasized malignant melanoma. Cancer, 117(10):2192-2201.

[18]GalonJ, BruniD, 2019. Approaches to treat immune hot, altered and cold tumours with combination immunotherapies. Nat Rev Drug Discov, 18(3):197-218.

[19]GongC, QiT, WeiX, et al., 2013. Thermosensitive polymeric hydrogels as drug delivery systems. Curr Med Chem, 20(1):79-94.

[20]GrodeL, SeilerP, BaumannS, et al., 2005. Increased vaccine efficacy against tuberculosis of recombinant Mycobacterium bovis bacille Calmette-Guérin mutants that secrete listeriolysin. J Clin Invest, 115(9):2472-2479.

[21]GrodeL, GanozaCA, BrohmC, et al., 2013. Safety and immunogenicity of the recombinant BCG vaccine VPM1002 in a phase 1 open-label randomized clinical trial. Vaccine, 31(9):1340-1348.

[22]JorakuA, HomhuanA, KawaiK, et al., 2009. Immunoprotection against murine bladder carcinoma by octaarginine-modified liposomes incorporating cell wall of Mycobacterium bovis bacillus Calmette-Guérin. BJU Int, 103(5):686-693.

[23]KawaiK, MiyazakiJ, JorakuA, et al., 2013. Bacillus Calmette-Guerin (BCG) immunotherapy for bladder cancer: current understanding and perspectives on engineered BCG vaccine. Cancer Sci, 104(1):22-27.

[24]KimHS, SeoHK, 2021. Emerging treatments for bacillus Calmette-Guérin-unresponsive non-muscle-invasive bladder cancer. Investig Clin Urol, 62(4):361-377.

[25]KimJH, ChoiJ, KimM, et al., 2022. Immunotherapeutic effects of recombinant Bacillus Calmette-Guérin containing sic gene in ex vivo and in vivo bladder cancer models. Investig Clin Urol, 63(2):228-237.

[26]KleinnijenhuisJ, QuintinJ, PreijersF, et al., 2014. Long-lasting effects of BCG vaccination on both heterologous Th1/Th17 responses and innate trained immunity. J Innate Immun, 6(2):152-158.

[27]KovácsM, HalfmannA, FedtkeI, et al., 2006. A functional dlt operon, encoding proteins required for incorporation of D-alanine in teichoic acids in gram-positive bacteria, confers resistance to cationic antimicrobial peptides in Streptococcus pneumoniae. J Bacteriol, 188(16):‍5797-5805.

[28]LaiR, JeyanathanM, ShalerCR, et al., 2014. Restoration of innate immune activation accelerates Th1-cell priming and protection following pulmonary mycobacterial infection. Eur J Immunol, 44(5):1375-1386.

[29]LammDL, ThorDE, HarrisSC, et al., 1980. Bacillus Calmette-Guerin immunotherapy of superficial bladder cancer. J Urol, 124(1):38-42.

[30]LammDL, van der MeijdenAPM, MoralesA, et al., 1992. Incidence and treatment of complications of bacillus Calmette-Guerin intravesical therapy in superficial bladder cancer. J Urol, 147(3):596-600.

[31]LarsenES, JoensenUN, PoulsenAM, et al., 2020. Bacillus Calmette-Guérin immunotherapy for bladder cancer: a review of immunological aspects, clinical effects and BCG infections. Apmis, 128(2):92-103.

[32]LeakakosT, JiC, LawsonG, et al., 2003. Intravesical administration of doxorubicin to swine bladder using magnetically targeted carriers. Cancer Chemother Pharmacol, 51(6):445-450.

[33]LiuL, ShenTT, LiuHF, et al., 2021. Toxicity effects of anthracycline-converted herceptin and azo-functionalized Fe3O4 nanoparticles on the heart of patients with breast cancer based on echocardiography. J Nanosci Nanotechnol, 21(2):878-885.

[34]LuoY, ChenXH, O'DonnellMA, 2003. Role of Th1 and Th2 cytokines in BCG-induced IFN-‍γ production: cytokine promotion and simulation of BCG effect. Cytokine, 21(1):17-26.

[35]LuoY, YamadaH, ChenX, et al., 2004. Recombinant Mycobacterium bovis bacillus Calmette-Guérin (BCG) expressing mouse IL-18 augments Th1 immunity and macrophage cytotoxicity. Clin Exp Immunol, 137(1):24-34.

[36]MaZ, DamaniaB, 2016. The cGAS-STING defense pathway and its counteraction by viruses. Cell Host Microbe, 19(2):150-158.

[37]MasudaH, NakamuraT, NomaY, et al., 2018. Application of BCG-CWS as a systemic adjuvant by using nanoparticulation technology. Mol Pharm, 15(12):5762-5771.

[38]MatsumotoM, SeyaT, KikkawaS, et al., 2001. Interferon gamma-producing ability in blood lymphocytes of patients with lung cancer through activation of the innate immune system by BCG cell wall skeleton. Int Immunopharmacol, 1(8):1559-1569.

[39]McBrideSM, SonensheinAL, 2011. The dlt operon confers resistance to cationic antimicrobial peptides in Clostridium difficile. Microbiology (Reading), 157(5):1457-1465.

[40]MedranoRFV, HungerA, MendonçaSA, et al., 2017. Immunomodulatory and antitumor effects of type I interferons and their application in cancer therapy. Oncotarget, 8(41):71249-71284.

[41]MiyazakiJ, KawaiK, KojimaT, et al., 2011a. The liposome-incorporating cell wall skeleton of Mycobacterium bovis bacillus Calmette-Guéin can directly enhance the susceptibility of cancer cells to lymphokine-activated killer cells through up-regulation of natural-killer group 2, member D ligands. BJU Int, 108(9):1520-1526.

[42]MiyazakiJ, NishiyamaH, YanoI, et al., 2011b. The therapeutic effects of R8-liposome-BCG-CWS on BBN-induced rat urinary bladder carcinoma. Anticancer Res, 31(6):‍2065-2071.

[43]MoralesA, 1978. Adjuvant immunotherapy in superficial bladder cancer. Natl Cancer Inst Monogr, 49:315-319.

[44]NakamuraT, FukiageM, HiguchiM, et al., 2014. Nanoparticulation of BCG-CWS for application to bladder cancer therapy. J Control Release, 176:44-53.

[45]NaveO, HareliS, ElbazM, et al., 2019. BCG and IL-2 model for bladder cancer treatment with fast and slow dynamics based on SPVF method‍—‍stability analysis. Math Biosci Eng, 16(5):5346-5379.

[46]NieuwenhuizenNE, KulkarniPS, ShaligramU, et al., 2017. The recombinant Bacille Calmette-Guérin vaccine VPM1002: ready for clinical efficacy testing. Front Immunol, 8:1147.

[47]NiranjanR, KoushikC, SaravananS, et al., 2013. A novel injectable temperature-sensitive zinc doped chitosan/β‍-glycerophosphate hydrogel for bone tissue engineering. Int J Biol Macromol, 54:24-29.

[48]OchiaiT, SatoH, HayashiR, et al., 1983. Postoperative adjuvant immunotherapy of gastric cancer with BCG-cell wall skeleton. 3- to 6-year follow up of a randomized clinical trial. Cancer Immunol Immunother, 14(3):167-171.

[49]ParkJ, FongPM, LuJ, et al., 2009. PEGylated PLGA nanoparticles for the improved delivery of doxorubicin. Nanomedicine, 5(4):410-418.

[50]PatardJJ, RodriguezA, LerayE, et al., 2002. Intravesical bacillus Calmette-Guerin treatment improves patient survival in T1G3 bladder tumours. Eur Urol, 41(6):635-642.

[51]PereraPY, LichyJH, WaldmannTA, et al., 2012. The role of interleukin-15 in inflammation and immune responses to infection: implications for its therapeutic use. Microbes Infect, 14(3):247-261.

[52]Pérez-JacoisteAsín MA, Fernández-RuizM, López-MedranoF, et al., 2014. Bacillus Calmette-Guérin (BCG) infection following intravesical BCG administration as adjunctive therapy for bladder cancer: incidence, risk factors, and outcome in a single-institution series and review of the literature. Medicine (Baltimore), 93(17):‍236-254.

[53]Redelman-SidiG, GlickmanMS, BochnerBH, 2014. The mechanism of action of BCG therapy for bladder cancer‍—a current perspective. Nat Rev Urol, 11(3):153-162.

[54]RentschCA, BosshardP, MayorG, et al., 2020. Results of the phase I open label clinical trial SAKK 06/14 assessing safety of intravesical instillation of VPM1002BC, a recombinant mycobacterium Bacillus Calmette Guérin (BCG), in patients with non-muscle invasive bladder cancer and previous failure of conventional BCG therapy. Oncoimmunology, 9(1):1748981.

[55]ShiWP, JiYW, ZhangXG, et al., 2011. Characterization of pH- and thermosensitive hydrogel as a vehicle for controlled protein delivery. J Pharm Sci, 100(3):886-895.

[56]SiegelRL, MillerKD, FuchsHE, et al., 2021. Cancer statistics, 2021. CA Cancer J Clin, 71(1):7-33.

[57]SinghAK, SrikrishnaG, BivalacquaTJ, et al., 2021. Recombinant BCGs for tuberculosis and bladder cancer. Vaccine, 39(50):7321-7331.

[58]SzokaF, 2008. The art of assembly. Science, 319(5863):‍578-579.

[59]TakeuchiA, EtoM, TatsugamiK, et al., 2016. Antitumor activity of recombinant Bacille Calmette-Guérin secreting interleukin-15-Ag85B fusion protein against bladder cancer. Int Immunopharmacol, 35:327-331.

[60]ThamSM, MahendranR, ChiongE, et al., 2020. Gmcsf and Ifnα gene therapy improves the response to BCG immunotherapy in a murine model of bladder cancer. Future Oncol, 16(17):1179-1188.

[61]TinhoferI, MarschitzI, HennT, et al., 2000. Expression of functional interleukin-15 receptor and autocrine production of interleukin-15 as mechanisms of tumor propagation in multiple myeloma. Blood, 95(2):610-618.

[62]TyagiP, LiZH, ChancellorM, et al., 2004. Sustained intravesical drug delivery using thermosensitive hydrogel. Pharm Res, 21(5):832-837.

[63]VerriWA, CunhaTM, FerreiraSH, et al., 2007. IL-15 mediates antigen-induced neutrophil migration by triggering IL-18 production. Eur J Immunol, 37(12):3373-3380.

[64]WaldmannTA, 2015. The shared and contrasting roles of IL2 and IL15 in the life and death of normal and neoplastic lymphocytes: implications for cancer therapy. Cancer Immunol Res, 3(3):219-227.

[65]WaldmannTA, LugliE, RoedererM, et al., 2011. Safety (toxicity), pharmacokinetics, immunogenicity, and impact on elements of the normal immune system of recombinant human IL-15 in rhesus macaques. Blood, 117(18):‍4787-4795.

[66]WangWX, ZhangP, ShanWG, et al., 2013. A novel chitosan-based thermosensitive hydrogel containing doxorubicin liposomes for topical cancer therapy. J Biomater Sci Polym Ed, 24(14):1649-1659.

[67]WangX, LiJ, WangYQ, et al., 2009. HFT-T, a targeting nanoparticle, enhances specific delivery of paclitaxel to folate receptor-positive tumors. ACS Nano, 3(10):‍3165-3174.

[68]World Health Organization, 2018. BCG vaccine: WHO position paper, February 2018 – Recommendations. Vaccine, 36(24):3408-3410.

[69]WuJJ, ZhaoL, HuHG, et al., 2020. Agonists and inhibitors of the STING pathway: potential agents for immunotherapy. Med Res Rev, 40(3):1117-1141.

[70]WurpelDJ, BeatsonSA, TotsikaM, et al., 2013. Chaperone-usher fimbriae of Escherichia coli. PLoS ONE, 8(1):e52835.

[71]YamadaH, MatsumotoS, MatsumotoT, et al., 2000. Murine IL-2 secreting recombinant Bacillus Calmette-Guerin augments macrophage-mediated cytotoxicity against murine bladder cancer MBT-2. J Urol, 164(2):526-531.

[72]YamamotoS, TsukamotoT, TeraiA, et al., 1997. Genetic evidence supporting the fecal-perineal-urethral hypothesis in cystitis caused by Escherichia coli. J Urol, 157(3):1127-1129.

[73]ZaharoffDA, HoffmanBS, HooperHB, et al., 2009. Intravesical immunotherapy of superficial bladder cancer with chitosan/interleukin-12. Cancer Res, 69(15):6192-6199.

[74]ZhangD, SunP, LiP, et al., 2013. A magnetic chitosan hydrogel for sustained and prolonged delivery of Bacillus Calmette-Guérin in the treatment of bladder cancer. Biomaterials, 34(38):10258-10266.

[75]ZhangL, GuFX, ChanJM, et al., 2008. Nanoparticles in medicine: therapeutic applications and developments. Clin Pharmacol Ther, 83(5):761-769.

[76]ZhangW, XuL, ParkHB, et al., 2020. Escherichia coli adhesion portion FimH functions as an adjuvant for cancer immunotherapy. Nat Commun, 11:1187.

[77]ZhangY, HuoF, CaoQ, et al., 2022. FimH confers mannose-targeting ability to Bacillus Calmette-Guerin for improved immunotherapy in bladder cancer. J Immunother Cancer, 10(3):e003939.

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