Principles bacterial immunotherapy
Bacterial immunotherapy treatment consists of (locally) administering bacterial products to an affected cancer patient with the goal of triggering an immune response against both the bacteria as well as cancer cells.
The working mechanism of for instance BCG treatment for bladder cancer is complex and involves both the innate and adaptive immune systems. Important constituents of the immune response to BCG include so-called CD4+ and CD8+ lymphocytes, natural killer cells, and granulocytes as well as TRAIL (tumour necrosis factor-related apoptosis-inducing ligand), IL-2, IL-8, IL-18, IL-12, interferon (IFN)-γ, and tumour necrosis factor (TNF).
Just as individual patients will respond differently to a given pathogen, the mechanism of action of bacterial immunotherapy is expected to vary depending on a patient’s own immune machinery and the characteristics of his/her tumour.
- Antonelli AC, Binyamin A, Hohl TM, Glickman MS, Redelman-Sidi G. Bacterial immunotherapy for cancer induces CD4-dependent tumor-specific immunity through tumor-intrinsic interferon-γ signaling. Proc Natl Acad Sci U S A. 2020 Aug 4;117(31):18627-18637. doi: 10.1073/pnas.2004421117. Epub 2020 Jul 17. PMID: 32680964; PMCID: PMC7414065.
- Patard JJ, Saint F, Velotti F, Abbou CC, Chopin DK. Immune response following intravesical bacillus Calmette-Guerin instillations in superficial bladder cancer: a review. Urol Res. 1998;26(3):155-9. doi: 10.1007/s002400050039. PMID: 9694595.
- Esteso G, Felgueres MJ, García-Jiménez ÁF, Reyburn-Valés C, Benguría A, Vázquez E, Reyburn HT, Aguiló N, Martín C, Puentes E, Murillo I, Rodríguez E, Valés-Gómez M. BCG-activation of leukocytes is sufficient for the generation of donor-independent innate anti-tumor NK and γδ T-cells that can be further expanded in vitro. Oncoimmunology. 2022 Dec 22;12(1):2160094. doi: 10.1080/2162402X.2022.2160094. PMID: 36567803; PMCID: PMC9788708.
- Chakrabarty AM. Microorganisms and cancer: quest for a therapy. J Bacteriol. 2003 May;185(9):2683-6.
- Andrew O. Yam, Jacqueline Bailey, Francis Lin, Arnolda Jakovija, Scott E. Youlten, Claudio Counoupas, Matthias Gunzer, Tobias Bald, Trent M. Woodruff, James A. Triccas, Leonard D. Goldstein, David Gallego-Ortega, Shane T. Grey, Tatyana Chtanova; Neutrophil conversion to a tumor-killing phenotype underpins effective microbial therapy. Cancer Res 2023;
- van Puffelen JH, Novakovic B, van Emst L, et al. Intravesical BCG in patients with non-muscle invasive bladder cancer induces trained immunity and decreases respiratory infections. Journal for ImmunoTherapy of Cancer 2023;11:e005518. doi:10.1136/ jitc-2022-005518
- Cancer Research UK: what is immunotherapy?
- National Cancer Institute: Immunotherapy: How the Immune System Fights Cancer
- Redelman-Sidi, G., Glickman, M. & Bochner, B. The mechanism of action of BCG therapy for bladder cancer—a current perspective. Nat Rev Urol 11, 153-162 (2014).
- Huang X, Pan J, Xu F, Shao B, Wang Y, Guo X, Zhou S. Bacteria-Based Cancer Immunotherapy. Adv Sci (Weinh). 2021 Feb 10;8(7):2003572.
- Cancer Research UK: BCG into the bladder
- BCG Treatment: What It Is, Procedure & Side Effects (clevelandclinic.org)