|
1
|
Jani CT, Manoharan A, DeMaria PJ, Bilusic M. Harnessing live vectors for cancer vaccines: Advancing therapeutic immunotherapy. Hum Vaccin Immunother 2025; 21:2469416. [PMID: 40127471 PMCID: PMC11934169 DOI: 10.1080/21645515.2025.2469416] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Revised: 02/03/2025] [Accepted: 02/16/2025] [Indexed: 03/26/2025] Open
Abstract
Cancer vaccines represent a promising approach within immunotherapies. These vaccines are tailored to target tumor-specific antigens, thereby offering a precision approach to cancer treatment. The key principles in developing therapeutic cancer vaccines include identifying appropriate vaccine targets and selecting effective vaccine delivery platforms. These delivery platforms are diverse and have evolved to enhance the immune response. This review explores live cancer vaccines and the biological entities involved. Live cancer vaccines leverage the use of various biological entities to stimulate an immune response. These biological entities including bacterial, yeast-based and viral vectors, have unique properties that can be harnessed to target and destroy cancer cells while eliciting a robust immune response. Clinical trials of cancer vaccines are investigating standalone and combination treatment strategies in the prophylactic, adjuvant, and palliative settings. This review offers insights into the current oncologic vaccine landscape and potential future development.
Collapse
Affiliation(s)
- Chinmay T. Jani
- Sylvester Comprehensive Cancer Center, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA
| | - Aysswarya Manoharan
- Sylvester Comprehensive Cancer Center, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA
| | | | - Marijo Bilusic
- Sylvester Comprehensive Cancer Center, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA
| |
Collapse
|
|
2
|
Lima MZT, Bastos DA, Mattedi RL, Dzik C, Jardim DLF, Coelho R, Ribeiro-Filho LA, Cordeiro MD, Nahas WC, Mello ES, Amano MT, Inoue LT, Camargo AA. Infiltrating Natural Killer cells influence the efficacy of BCG immunotherapy in non-muscle-invasive bladder cancer. Pathol Res Pract 2025; 270:155997. [PMID: 40349568 DOI: 10.1016/j.prp.2025.155997] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2024] [Revised: 04/29/2025] [Accepted: 05/05/2025] [Indexed: 05/14/2025]
Abstract
Non-muscle-invasive bladder cancer (NMIBC) consists of tumors restricted to the bladder urothelium or lamina propria, without invasion of the muscular layer. Intravesical BCG (Bacillus Calmette-Guérin) is widely used as an adjuvant therapy for patients with intermediate or high-risk NMIBC. However, a significant proportion of these patients fail to respond to BCG or recur after treatment. Moreover, despite decades of BCG usage, there are still no clinically validated biomarkers capable of predicting which patients will benefit from this treatment. Emerging evidence suggests that the tumor immune microenvironment influences the efficacy of BCG immunotherapy. In this context, our study aimed to assess, by immunohistochemistry, whether the abundance of immune cell subpopulations - Natural Killer (NK) cells, tumor-associated macrophages (TAMs), CD4 + T, CD8 + T, and FOXP3 + regulatory T (Treg) cells, or T cell ratios (CD4 +/CD8 + and FOXP3 +/CD8 +) - in NMIBC urothelium, prior to BCG, were associated with BCG response rate (RR) and recurrence-free survival (RFS) after treatment. We demonstrated that higher pretreatment NK cell count in the NMIBC urothelium is significantly associated with improved BCG RR and prolonged RFS after BCG immunotherapy. We hypothesize these results are associated with BCG-induced trained immunity, which has been proposed to be essential for the efficacy of BCG immunotherapy in bladder cancer. Once validated and further investigated by future studies, our findings may help to improve the stratification and treatment of patients with NMIBC.
Collapse
Affiliation(s)
| | - Diogo A Bastos
- Hospital Sírio-Libanês, São Paulo, SP, Brazil; Instituto do Câncer do Estado de São Paulo (ICESP), São Paulo, SP, Brazil
| | - Romulo L Mattedi
- Hospital Sírio-Libanês, São Paulo, SP, Brazil; Instituto do Câncer do Estado de São Paulo (ICESP), São Paulo, SP, Brazil.
| | - Carlos Dzik
- Instituto do Câncer do Estado de São Paulo (ICESP), São Paulo, SP, Brazil
| | | | - Rafael Coelho
- Instituto do Câncer do Estado de São Paulo (ICESP), São Paulo, SP, Brazil.
| | | | | | - William C Nahas
- Instituto do Câncer do Estado de São Paulo (ICESP), São Paulo, SP, Brazil.
| | - Evandro S Mello
- Instituto do Câncer do Estado de São Paulo (ICESP), São Paulo, SP, Brazil.
| | | | | | | |
Collapse
|
|
3
|
Liang L, Chen D, Han M, Liu LR, Luo L, Yue J. Impact of IL-32 gene polymorphisms on tuberculosis susceptibility in a Chinese Han population. Microb Pathog 2025; 200:107313. [PMID: 39842733 DOI: 10.1016/j.micpath.2025.107313] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2024] [Revised: 12/26/2024] [Accepted: 01/18/2025] [Indexed: 01/24/2025]
Abstract
OBJECTIVE Interleukin (IL)-32, encoded by the IL-32 gene, is a crucial constituent of the autophagy pathway and is involved in the regulation of Mycobacterium tuberculosis (M.tb) infection, a major global health challenge. This study aimed to examine the potential association between IL-32 polymorphisms and susceptibility to Tuberculosis(TB), highlighting the significance of genetic factors in TB risk. DESIGN Sequence analysis of IL-32 was conducted in 570 individuals diagnosed with pulmonary tuberculosis (PTB), 363 individuals diagnosed with extrapulmonary tuberculosis (EPTB), and 604 healthy controls from the Chinese Han population, representing a broad spectrum of TB manifestations. Five single nucleotide polymorphisms(SNPs) were selected for analysis based on their potential impact on IL-32 function and TB susceptibility. RESULTS The study revealed that the polymorphism rs12934561C allele exhibits a positive correlation with elevated susceptibility to PTB (P = 0.003, OR (95%CI) = 1.28 (1.09-1.51)), highlighting its potential role as a biomarker for PTB risk. A noteworthy relationship was observed between the rs12934561 TT genotype and the decreased likelihood of PTB, further underscoring the complexity of IL-32's role in PTB susceptibility. Moreover, it was found that protective haplotypes for PTB are TCAAC (P = 0.001, OR (95%CI) = 0.75 (0.62-0.90)) and TCGTT (P = 0.002, OR (95%CI) = 0.47 (0.29-0.77)) may be present in IL-32; Conversely, the potential risk haplotypes for PTB are CCGAA (P = 0.007, OR (95%CI) = 1.29 (1.07-1.55)) and TCATT (P = 0.033, OR (95%CI) = 1.30 (1.02-1.66)), indicating genetic variations that increase PTB susceptibility. In contrast, neither allelic nor genotypic associations were statistically significant among EPTB cases, highlighting the distinct genetic influences on the different forms of TB. CONCLUSION In this study, we discovered that polymorphisms in IL-32 are significantly associated with increased susceptibility to pulmonary TB. This finding underscores the crucial role of genetic variation in the development of TB and provides a potential avenue for targeted interventions.
Collapse
Affiliation(s)
- Li Liang
- Department of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China
| | - DaWen Chen
- Center of Clinical Laboratory Medicine, Zhongda Hospital, Southeast University, Nanjing, China
| | - Min Han
- Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China
| | - Li-Rong Liu
- Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China
| | - LiuLin Luo
- Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China.
| | - Jun Yue
- Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China.
| |
Collapse
|
|
4
|
Naqvi N, Ahuja Y, Zarin S, Alam A, Ali W, Shariq M, Hasnain SE, Ehtesham NZ. BCG's role in strengthening immune responses: Implications for tuberculosis and comorbid diseases. INFECTION, GENETICS AND EVOLUTION : JOURNAL OF MOLECULAR EPIDEMIOLOGY AND EVOLUTIONARY GENETICS IN INFECTIOUS DISEASES 2025; 127:105703. [PMID: 39667418 DOI: 10.1016/j.meegid.2024.105703] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Revised: 10/20/2024] [Accepted: 12/06/2024] [Indexed: 12/14/2024]
Abstract
The BCG vaccine represents a significant milestone in the prevention of tuberculosis (TB), particularly in children. Researchers have been developing recombinant BCG (rBCG) variants that can trigger lasting memory responses, thereby enhancing protection against TB in adults. The breakdown of immune surveillance is a key link between TB and other communicable and non-communicable diseases. Notably, TB is more prevalent among people with comorbidities such as HIV, diabetes, cancer, influenza, COVID-19, and autoimmune disorders. rBCG formulations have the potential to address both TB and HIV co-pandemics. TB increases the risk of lung cancer and immunosuppression caused by cancer can reactivate latent TB infections. Moreover, BCG's efficacy extends to bladder cancer treatment and blood glucose regulation in patients with diabetes and TB. Additionally, BCG provides cross-protection against unrelated pathogens, emphasizing the importance of BCG-induced trained immunity in COVID-19 and other respiratory diseases. Furthermore, BCG reduced the severity of pulmonary TB-induced influenza virus infections. Recent studies have proposed innovations in BCG delivery, revaccination, and attenuation techniques. Disease-centered research has highlighted the immunomodulatory effects of BCG on TB, HIV, cancer, diabetes, COVID-19, and autoimmune diseases. The complex relationship between TB and comorbidities requires a nuanced re-evaluation to understand the shared attributes regulated by BCG. This review assessed the interconnected relationships influenced by BCG administration in TB and related disorders, recommending the expanded use of rBCG in healthcare. Collaboration among vaccine research stakeholders is vital to enhance BCG's efficacy against global health challenges.
Collapse
Affiliation(s)
- Nilofer Naqvi
- Department of Life Sciences, Sharda School of Basic Sciences and Research, Sharda University, Knowledge Park III, Greater Noida, Uttar Pradesh 201306, India
| | - Yashika Ahuja
- Department of Life Sciences, Sharda School of Basic Sciences and Research, Sharda University, Knowledge Park III, Greater Noida, Uttar Pradesh 201306, India
| | - Sheeba Zarin
- Department of Life Sciences, Sharda School of Basic Sciences and Research, Sharda University, Knowledge Park III, Greater Noida, Uttar Pradesh 201306, India
| | - Anwar Alam
- Department of Life Sciences, Sharda School of Basic Sciences and Research, Sharda University, Knowledge Park III, Greater Noida, Uttar Pradesh 201306, India
| | - Waseem Ali
- Department of Life Sciences, Sharda School of Basic Sciences and Research, Sharda University, Knowledge Park III, Greater Noida, Uttar Pradesh 201306, India
| | - Mohd Shariq
- GITAM School of Science, GITAM University, Rudraram, Hyderabad Campus, Telangana 502329, India
| | - Seyed E Hasnain
- Department of Life Sciences, Sharda School of Basic Sciences and Research, Sharda University, Knowledge Park III, Greater Noida, Uttar Pradesh 201306, India; Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology, Delhi (IIT-D), Hauz Khas, New Delhi 110 016, India..
| | - Nasreen Z Ehtesham
- Department of Life Sciences, Sharda School of Basic Sciences and Research, Sharda University, Knowledge Park III, Greater Noida, Uttar Pradesh 201306, India.
| |
Collapse
|
|
5
|
Zhao X, Qi X, Liu D, Che X, Wu G. A Novel Approach for Bladder Cancer Treatment: Nanoparticles as a Drug Delivery System. Int J Nanomedicine 2024; 19:13461-13483. [PMID: 39713223 PMCID: PMC11662911 DOI: 10.2147/ijn.s498729] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Accepted: 12/05/2024] [Indexed: 12/24/2024] Open
Abstract
Bladder cancer represents one of the most prevalent malignant neoplasms of the urinary tract. In the Asian context, it represents the eighth most common cancer in males. In 2022, there were approximately 613,791 individuals diagnosed with bladder cancer worldwide. Despite the availability of efficacious treatments for the two principal forms of bladder cancer, namely non-invasive and invasive bladder cancer, the high incidence of recurrence following treatment and the suboptimal outcomes observed in patients with high-grade and advanced disease represent significant concerns in the management of bladder cancer at this juncture. Nanoparticles have gained attention for their excellent properties, including stable physical properties, a porous structure that can be loaded with a variety of substances, and so on. The in-depth research on nanoparticles has led to their emergence as a new class of nanoparticles for combination therapy, due to their advantageous properties. These include the extension of the drug release window, the enhancement of drug bioavailability, the improvement of drug targeting ability, the reduction of local and systemic toxicity, and the simultaneous delivery of multiple drugs for combination therapy. As a result, nanoparticles have become a novel agent of the drug delivery system. The advent of nanoparticles has provided a new impetus for the development of non-surgical treatments for bladder cancer, including chemotherapy, immunotherapy, gene therapy and phototherapy. The unique properties of nanoparticles have facilitated the combination of diverse non-surgical therapeutic modalities, enhancing their overall efficacy. This review examines the recent advancements in the use of nanoparticles in non-surgical bladder cancer treatments, encompassing aspects such as delivery, therapeutic efficacy, and the associated toxicity of nanoparticles, as well as the challenges encountered in clinical applications.
Collapse
Affiliation(s)
- Xinming Zhao
- Department of Urology, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, People’s Republic of China
| | - Xiaochen Qi
- Department of Urology, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, People’s Republic of China
| | - Dequan Liu
- Department of Urology, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, People’s Republic of China
| | - Xiangyu Che
- Department of Urology, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, People’s Republic of China
| | - Guangzhen Wu
- Department of Urology, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, People’s Republic of China
| |
Collapse
|
|
6
|
Kunjalwar R, Keerti A, Chaudhari A, Sahoo K, Meshram S. Microbial Therapeutics in Oncology: A Comprehensive Review of Bacterial Role in Cancer Treatment. Cureus 2024; 16:e70920. [PMID: 39502977 PMCID: PMC11535891 DOI: 10.7759/cureus.70920] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Accepted: 10/05/2024] [Indexed: 11/08/2024] Open
Abstract
Conventional cancer therapies, including chemotherapy, radiotherapy, and immunotherapy, have significantly advanced cancer treatment. However, these modalities often face limitations such as systemic toxicity, lack of specificity, and the emergence of resistance. Recent advancements in genetic engineering and synthetic biology have rekindled interest in using bacteria as a novel therapeutic approach in oncology. This comprehensive review explores the potential of microbial therapeutics, particularly bacterial therapies, in the treatment of cancer. Bacterial therapies offer several unique advantages, such as the ability to selectively target and colonize hypoxic and necrotic regions of tumors, areas typically resistant to conventional treatments. The review delves into the mechanisms through which bacteria exert antitumor effects, including direct tumor cell lysis, modulation of the immune response, and delivery of therapeutic agents like cytotoxins and enzymes. Various bacterial species, such as Salmonella, Clostridium, Lactobacillus, and Listeria, have shown promise in preclinical and clinical studies, demonstrating diverse mechanisms of action and therapeutic potential. Moreover, the review discusses the challenges associated with bacterial therapies, such as safety concerns, immune evasion, and the need for precise targeting, and how recent advances in genetic engineering are being used to overcome these hurdles. Current clinical trials and combination strategies with conventional therapies are also highlighted to provide a comprehensive overview of the ongoing developments in this field. In conclusion, while bacterial therapeutics present a novel and promising avenue in cancer treatment, further research and clinical validation is required to fully realize their potential. This review aims to inspire further exploration into microbial oncology, paving the way for innovative and more effective cancer therapies.
Collapse
Affiliation(s)
- Radha Kunjalwar
- Microbiology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Akshunna Keerti
- Internal Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Achal Chaudhari
- Microbiology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Kaushik Sahoo
- Microbiology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Supriya Meshram
- Microbiology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| |
Collapse
|
|
7
|
Noel OD, Hassouneh Z, Svatek RS, Mukherjee N. Innate Lymphoid Cells in Bladder Cancer: From Mechanisms of Action to Immune Therapies. Cancer Immunol Res 2024; 12:149-160. [PMID: 38060011 PMCID: PMC11492724 DOI: 10.1158/2326-6066.cir-23-0414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Revised: 07/10/2023] [Accepted: 10/24/2023] [Indexed: 12/08/2023]
Abstract
Bladder tumors have a high mutational burden and tend to be responsive to immune therapies; however, response rates remain modest. To date, immunotherapy in bladder cancer has largely focused on enhancing T-cell immune responses in the bladder tumor microenvironment. It is anticipated that other immune cells, including innate lymphoid cells (ILC), which play an important role in bladder oncogenesis and tumor suppression, could be targeted to improve response to existing therapies. ILCs are classified into five groups: natural killer cells, ILC1s, ILC2s, ILC3s, and lymphoid tissue inducer cells. ILCs are pleiotropic and play dual and sometimes paradoxical roles in cancer development and progression. Here, a comprehensive discussion of the current knowledge and recent advancements in understanding the role of ILCs in bladder cancer is provided. We discuss the multifaceted roles that ILCs play in bladder immune surveillance, tumor protection, and immunopathology of bladder cancer. This review provides a rationale for targeting ILCs in bladder cancer, which is relevant for other solid tumors.
Collapse
Affiliation(s)
- Onika D.V. Noel
- Department of Urology, University of Texas Health San Antonio, San Antonio, Texas
| | - Zaineb Hassouneh
- Department of Microbiology, Immunology & Molecular Genetics, University of Texas Health San Antonio, San Antonio, Texas
| | - Robert S. Svatek
- Department of Urology, University of Texas Health San Antonio, San Antonio, Texas
| | - Neelam Mukherjee
- Department of Urology, University of Texas Health San Antonio, San Antonio, Texas
| |
Collapse
|
|
8
|
Weng J, Yang J, Wang W, Wen J, Fang M, Zheng G, Xie J, Zheng X, Feng L, Yan Q. Application of microneedles combined with dendritic cell-targeted nanovaccine delivery system in percutaneous immunotherapy for triple-negative breast cancer. NANOTECHNOLOGY 2023; 34:475101. [PMID: 37478829 DOI: 10.1088/1361-6528/ace97b] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Accepted: 07/21/2023] [Indexed: 07/23/2023]
Abstract
This work aims at developing a strategy to activate the antigen-presenting cells to enhance the effect of immunotherapy in triple-negative breast cancer (TNBC) through the dissolving microneedle patch (DMNP). In present study, mannosylated chitosan (MCS) nanoparticles (NPs) were designed to target dendritic cells (DCs), and the immunotherapy effect was enhanced by the adjuvant Bacillus Calmette-Guerin polysaccharide (BCG-PSN), achieving the purpose of transdermal immunotherapy for TNBC. Vaccination studies with mice demonstrated that MCS NPs effectively induce DCs maturation in the tumor-draining lymph nodes to stimulate strong immune responses in TNBC. Overall, chitosan-based DMNPs with complex adjuvant constituted a new potent transdermal vaccine delivery platform capable of exploiting more DCs in the skin for effective immunization.
Collapse
Affiliation(s)
- Jiaqi Weng
- College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, People's Republic of China
| | - Jing Yang
- College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, People's Republic of China
| | - Weiwei Wang
- College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, People's Republic of China
| | - Jiaoli Wen
- College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, People's Republic of China
| | - Min Fang
- College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, People's Republic of China
| | - Gensuo Zheng
- College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, People's Republic of China
| | - Jing Xie
- Third Clinical College of Wenzhou Medical University, Wenzhou People's Hospital, Wenzhou 325000, People's Republic of China
| | - Xi Zheng
- Analysis Center of Agrobiology and Environmental Sciences, Zhejiang University, Hangzhou 310058, People's Republic of China
| | - Lili Feng
- Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, People's Republic of China
| | - Qinying Yan
- College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, People's Republic of China
| |
Collapse
|
|
9
|
Föhse K, Debisarun PA, Kilic G, van Dodewaard-de Jong JM, Netea MG. Evaluation of the safety and immunological effects of Bacillus Calmette-Guérin in combination with checkpoint inhibitor therapy in a patient with neuroendocrine carcinoma: a case report. J Med Case Rep 2023; 17:377. [PMID: 37661259 PMCID: PMC10476294 DOI: 10.1186/s13256-023-04117-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Accepted: 08/03/2023] [Indexed: 09/05/2023] Open
Abstract
BACKGROUND Immune checkpoint inhibitors have revolutionized therapy of advanced and metastatic cancers. However, a significant proportion of patients do not respond to immune checkpoint inhibitors or develop resistance. Therefore, novel therapies or combinations of therapies that may act synergistically are needed. It has been suggested that induction of trained immunity may increase the response to immune checkpoint inhibitor therapy, through reprogramming myeloid cells toward an antitumor phenotype. On the other hand, activation of the immune system also carries the risk of potentially sustaining tumorgenicity and increasing immune- related toxicity. CASE PRESENTATION We report the case of a 37-year-old Dutch male suffering from gastric neuroendocrine carcinoma with liver metastases and high risk for an unfavorable outcome, who was treated with a combination of programmed cell death protein 1 inhibitor nivolumab and the trained immunity-inducer Bacillus Calmette-Guérin vaccine as a salvage therapy. Three doses of BCG vaccine were administered at 3-month intervals, in conjunction with the immune checkpoint inhibitor regimen. At a certain point, radiation therapy was added to the treatment regimen. During the combination of these therapies, the patient developed immune-mediated colitis, which necessitated discontinuation of all treatments. Bacillus Calmette-Guérin vaccination induced a trained immune response with elevated monocyte-derived interleukin-6 and interleukin-1β production capacity. From the first vaccination with Bacillus Calmette-Guérin until 3 months after the last vaccination with Bacillus Calmette-Guérin, the patient displayed only mild progression of the primary tumor and no progression of the metastases. CONCLUSION In this study, we show the feasibility to combine checkpoint inhibitor therapy with inducers of trained immunity in a patient with an aggressive neuroendocrine tumor. Autoimmune side effects are common under programmed cell death protein 1 inhibitor therapy, which was considered the most likely cause of colitis, although an additive effect of Bacillus Calmette-Guérin vaccination or radiotherapy cannot be excluded. The patient displayed only mild progression during the combination therapy, but larger studies are warranted to fully explore the potential benefit of trained immunity inducers as an adjuvant to immune checkpoint inhibitor therapy.
Collapse
Affiliation(s)
- Konstantin Föhse
- Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
- Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Priya A Debisarun
- Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
- Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Gizem Kilic
- Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
- Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | | | - Mihai G Netea
- Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
- Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
- Department for Genomics & Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany.
| |
Collapse
|
|
10
|
MacDonald A, Mehrnoush V, Ismail A, Di Matteo L, Zakaria A, Shabana W, Shaban A, Bassuony M, Elmansy H, Shahrour W, Prowse O, Kotb A. History of infantile BCG immunization did not predict lamina propria invasion and/or high-grade in patients with non-muscle invasive bladder cancer. Arch Ital Urol Androl 2023:11380. [PMID: 37259815 DOI: 10.4081/aiua.2023.11380] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Accepted: 05/26/2023] [Indexed: 06/02/2023] Open
Abstract
OBJECTIVE To evaluate the utility of infantile BCG vaccination history in predicting stage and grade of tumours in non-muscle invasive bladder cancer (NMIBC). MATERIALS AND METHODS We retrospectively analyzed data from patients from a single center who were diagnosed with new NMIBC and underwent transurethral resection of bladder tumour (TURBT) between 2017 and 2022. We assessed BCG immunization status with various demographics and comorbidities, as well as tumour recurrence, progression, stage, and grade. RESULTS A total of 188 patients met the inclusion criteria for our study. The mean age of patients at the time of diagnosis was significantly lower in those that had been immunized with BCG (71 ± 9) than those who had not (77 ± 10) (p < 0.0001). History of BCG immunization did not correlate with sex, history of diabetes mellitus (DM), prior history of intravesical BCG treatment, and tumour recurrence, progression, stage, and grade. CONCLUSIONS History of infantile BCG vaccination did not correlate with the depth of invasion and/or the grade in patients with non-muscle invasive bladder cancer. Patients that received infantile BCG vaccination were significantly younger at the time of diagnosis of NMIBC.
Collapse
Affiliation(s)
| | | | - Asmaa Ismail
- Northern Ontario School of Medicine, Thunder Bay, ON.
| | - Livio Di Matteo
- Department of Economics, Lakehead University, Thunder Bay, ON.
| | - Ahmed Zakaria
- Northern Ontario School of Medicine, Thunder Bay, ON.
| | | | - Ashraf Shaban
- Northern Ontario School of Medicine, Thunder Bay, ON.
| | | | - Hazem Elmansy
- Northern Ontario School of Medicine, Thunder Bay, ON.
| | | | - Owen Prowse
- Northern Ontario School of Medicine, Thunder Bay, ON.
| | - Ahmed Kotb
- Northern Ontario School of Medicine, Thunder Bay, ON.
| |
Collapse
|
|
11
|
Yao Y, Ji JJ, Wang HY, Sun LJ, Zhang GM. Granulomatous prostatitis after bacille Calmette-Guérin instillation resembles prostate carcinoma: A case report and review of the literature. World J Clin Cases 2023; 11:2051-2059. [PMID: 36998956 PMCID: PMC10044953 DOI: 10.12998/wjcc.v11.i9.2051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2022] [Revised: 01/15/2023] [Accepted: 03/01/2023] [Indexed: 03/16/2023] Open
Abstract
BACKGROUND Bacille Calmette-Guérin (BCG) instillation is recommended in patients with non-muscle-invasive bladder cancer who have intermediate-risk and high-risk tumors. However, granulomatous prostatitis is a rare complication induced by BCG instillation, which can easily be misdiagnosed as prostate cancer. Here, we report a case of granulomatous prostatitis that resembled prostate cancer.
CASE SUMMARY A 64-year-old Chinese man with bladder cancer received BCG instillation. Three days later, he stopped BCG instillation and received anti-infective therapy due to the urinary tract infection. Three months after BCG restart, he had rising total prostate-specific antigen (PSA) (9.14 ng/mL) and decreasing free PSA/total PSA (0.09). T2-weighted images of magnetic resonance imaging (MRI) showed a 28 mm × 20 mm diffuse low signal abnormality in the right peripheral zone, which was markedly hyperintense on high b-value diffusion-weighted MRI and hypointense on apparent diffusion coefficient map images. Considering Prostate Imaging Reporting and Data System score of 5 and possibility of prostate cancer, a prostate biopsy was conducted. Histopathology showed typical features of granulomatous prostatitis. The nucleic acid test for tuberculosis was positive. He was finally diagnosed with BCG-induced granulomatous prostatitis. Thereafter, he stopped BCG instillation and received anti-tuberculosis treatment. During 10 mo follow-up, he had no evidence of tumor recurrence or symptoms of tuberculosis.
CONCLUSION Temporarily elevated PSA and high followed by low signal abnormality on diffusion-weighted MRI are important indicators of BCG-induced granulomatous prostatitis.
Collapse
Affiliation(s)
- Yu Yao
- Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, China
| | - Jun-Jie Ji
- Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, China
| | - Hai-Yun Wang
- Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, China
| | - Li-Jiang Sun
- Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, China
| | - Gui-Ming Zhang
- Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, China
| |
Collapse
|
|
12
|
Wang J, Guo N, Hou W, Qin H. Coating bacteria for anti-tumor therapy. Front Bioeng Biotechnol 2022; 10:1020020. [PMID: 36185433 PMCID: PMC9520470 DOI: 10.3389/fbioe.2022.1020020] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Accepted: 09/01/2022] [Indexed: 11/13/2022] Open
Abstract
Therapeutic bacteria have shown great potential on anti-tumor therapy. Compared with traditional therapeutic strategy, living bacteria present unique advantages. Bacteria show high targeting and great colonization ability in tumor microenvironment with hypoxic and nutritious conditions. Bacterial-medicated antitumor therapy has been successfully applied on mouse models, but the low therapeutic effect and biosafe limit its application on clinical treatment. With the development of material science, coating living bacteria with suitable materials has received widespread attention to achieve synergetic therapy on tumor. In this review, we summarize various materials for coating living bacteria in cancer therapy and envision the opportunities and challenges of bacteria-medicated antitumor therapy.
Collapse
Affiliation(s)
- Jiahui Wang
- Department of Gastrointestinal Surgery, Shanghai Tenth People’s Hospital, Tongji University, Shanghai, China
| | - Ning Guo
- Department of Gastrointestinal Surgery, Shanghai Tenth People’s Hospital, Tongji University, Shanghai, China
- *Correspondence: Ning Guo, ; Weiliang Hou, ; Huanlong Qin,
| | - Weiliang Hou
- Department of Gastrointestinal Surgery, Shanghai Tenth People’s Hospital, Tongji University, Shanghai, China
- Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Institute of Molecular Medicine, Renji Hospital School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- *Correspondence: Ning Guo, ; Weiliang Hou, ; Huanlong Qin,
| | - Huanlong Qin
- Department of Gastrointestinal Surgery, Shanghai Tenth People’s Hospital, Tongji University, Shanghai, China
- *Correspondence: Ning Guo, ; Weiliang Hou, ; Huanlong Qin,
| |
Collapse
|
|
13
|
Tang Q, Peng X, Xu B, Zhou X, Chen J, Cheng L. Current Status and Future Directions of Bacteria-Based Immunotherapy. Front Immunol 2022; 13:911783. [PMID: 35757741 PMCID: PMC9226492 DOI: 10.3389/fimmu.2022.911783] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2022] [Accepted: 05/12/2022] [Indexed: 02/05/2023] Open
Abstract
With the in-depth understanding of the anti-cancer immunity, immunotherapy has become a promising cancer treatment after surgery, radiotherapy, and chemotherapy. As natural immunogenicity substances, some bacteria can preferentially colonize and proliferate inside tumor tissues to interact with the host and exert anti-tumor effect. However, further research is hampered by the infection-associated toxicity and their unpredictable behaviors in vivo. Due to modern advances in genetic engineering, synthetic biology, and material science, modifying bacteria to minimize the toxicity and constructing a bacteria-based immunotherapy platform has become a hotspot in recent research. This review will cover the inherent advantages of unedited bacteria, highlight how bacteria can be engineered to provide greater tumor-targeting properties, enhanced immune-modulation effect, and improved safety. Successful applications of engineered bacteria in cancer immunotherapy or as part of the combination therapy are discussed as well as the bacteria based immunotherapy in different cancer types. In the end, we highlight the future directions and potential opportunities of this emerging field.
Collapse
Affiliation(s)
- Quan Tang
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,Department of Operative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Xian Peng
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Bo Xu
- Cancer Institute, Xuzhou Medical University, Xuzhou, China.,Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Xuedong Zhou
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,Department of Operative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Jing Chen
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,Department of Operative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Lei Cheng
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,Department of Operative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| |
Collapse
|
|
14
|
After 100 Years of BCG Immunization against Tuberculosis, What Is New and Still Outstanding for This Vaccine? Vaccines (Basel) 2021; 10:vaccines10010057. [PMID: 35062718 PMCID: PMC8778337 DOI: 10.3390/vaccines10010057] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Revised: 12/17/2021] [Accepted: 12/29/2021] [Indexed: 12/14/2022] Open
Abstract
In 2021, most of the world was reasonably still concerned about the COVID-19 pandemic, how cases were up and down in different countries, how the vaccination campaigns were ongoing, and most people were familiar with the speed with which vaccines against SARS-Co-V2 were developed, analyzed, and started to be applied in an attempt to curb the pandemic. Because of this, it may have somehow passed relatively inadvertently for people outside of the field that the vaccine used to control tuberculosis (TB), Mycobacterium bovis Bacille Calmette-Guérin (BCG), was first applied to humans a century ago. Over these years, BCG has been the vaccine applied to most human beings in the world, despite its known lack of efficacy to fully prevent respiratory TB. Several strategies have been employed in the last 20 years to produce a novel vaccine that would replace, or boost, immunity and protection elicited by BCG. In this work, to avoid potential redundancies with recently published reviews, I only aim to present my current thoughts about some of the latest findings and outstanding questions that I consider worth investigating to help develop a replacement or modified BCG in order to successfully fight TB, based on BCG itself.
Collapse
|
|
15
|
|