Tue, Aug 25, 2026
[Archive]
Volume 18, Issue 1 (March-2026 2026)
Iranian Journal of Blood and Cancer 2026, 18(1): 102-113 |
Back to browse issues page
Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
Singh Matreja P, Kumar A, Kumar V, Singh S. Efficacy and Safety of Bacterial-Based Cancer Therapies: A Meta-Analysis of Preclinical and Clinical Studies. Iranian Journal of Blood and Cancer 2026; 18 (1) :102-113
URL: http://ijbc.ir/article-1-1760-en.html
URL: http://ijbc.ir/article-1-1760-en.html
1- Teerthanker Mahaveer Medical College and Research Centre, Teerthanker Mahaveer University, Moradabad, UP, India.
2- Teerthanker Mahaveer Medical College and Research Centre, Teerthanker Mahaveer University, Moradabad, UP, India. ,singhdrsudhir4@gmail.com
2- Teerthanker Mahaveer Medical College and Research Centre, Teerthanker Mahaveer University, Moradabad, UP, India. ,
Abstract: (510 Views)
Background: Cancer remains a major global health burden, and while conventional treatments like chemotherapy and immunotherapy have improved outcomes, they are limited by resistance and adverse effects. Bacterial-based cancer therapies (BBCTs) offer a promising alternative due to their tumor-targeting ability, immune modulation, and potential as therapeutic vectors.
Objective: This meta-analysis evaluates the efficacy and safety of BBCTs by analyzing tumor growth inhibition (TGI%) in preclinical models and progression-free survival (PFS), overall survival (OS), and optimal response rate (ORR) in clinical studies.
Methods: A systematic search of PubMed, Google Scholar, and Cochrane Library was conducted for relevant studies. Data on treatment efficacy and adverse events were extracted and statistically analyzed.
Results: BBCTs showed significant tumor suppression and survival benefits over controls. PFS consistently demonstrated tumor growth delay, and some OS values extended beyond 35 units, suggesting long-term benefit. However, variability in outcomes was noted, influenced by bacterial strain, tumor type, and immune response. Safety concerns, including toxicity and immune-related effects, were also observed.
Conclusion: BBCTs show strong therapeutic promise, but further clinical validation is needed to improve delivery, consistency, and safety. Personalized, translational research is key to bridging preclinical findings with clinical application.
: Meta-analysis |
Subject:
Infectious Diseases
Received: 2025/12/26 | Accepted: 2026/03/10 | Published: 2026/03/31
Received: 2025/12/26 | Accepted: 2026/03/10 | Published: 2026/03/31
References
1. Gupta, K. H.; Nowicki, C.; Giurini, E. F.; Marzo, A. L.; Zloza, A. Bacterial-Based Cancer Therapy (BBCT): Recent Advances, Current Challenges, and Future Prospects for Cancer Immunotherapy. Vaccines 2021, 9 (12), 1497. [DOI:10.3390/vaccines9121497]
2. Kwon, S.-Y.; Thi-Thu Ngo, H.; Son, J.; Hong, Y.; Min, J.-J. Exploiting Bacteria for Cancer Immunotherapy. Nat Rev Clin Oncol 2024, 21 (8), 569-589. [DOI:10.1038/s41571-024-00908-9]
3. Sieow, B. F.-L.; Wun, K. S.; Yong, W. P.; Hwang, I. Y.; Chang, M. W. Tweak to Treat:Reprograming Bacteria for Cancer Treatment. Trends Cancer 2021, 7 (5), 447-464. [DOI:10.1016/j.trecan.2020.11.004]
4. Lu, J.; Tong, Q. From Pathogenesis to Treatment: The Impact of Bacteria on Cancer. Front. Microbiol. 2024, 15, 1462749. [DOI:10.3389/fmicb.2024.1462749]
5. Duong, M. T.-Q.; Qin, Y.; You, S.-H.; Min, J.-J. Bacteria-Cancer Interactions: Bacteria-Based Cancer Therapy. Exp Mol Med 2019, 51 (12), 1-15. [DOI:10.1038/s12276-019-0297-0]
6. Sedighi, M.; Zahedi Bialvaei, A.; Hamblin, M. R.; Ohadi, E.; Asadi, A.; Halajzadeh, M.; Lohrasbi, V.; Mohammadzadeh, N.; Amiriani, T.; Krutova, M.; Amini, A.; Kouhsari, E.Therapeutic Bacteria to Combat Cancer; Current Advances, Challenges, and Opportunities. Cancer Medicine 2019, 8 (6), 3167-3181. [DOI:10.1002/cam4.2148]
7. Liang, S.; Wang, C.; Shao, Y.; Wang, Y.; Xing, D.; Geng, Z. Recent Advances in BacteriaMediated Cancer Therapy. Front. Bioeng. Biotechnol. 2022, 10, 1026248. [DOI:10.3389/fbioe.2022.1026248]
8. Song, S.; Vuai, M. S.; Zhong, M. The Role of Bacteria in Cancer Therapy - Enemies in the Past, but Allies at Present. Infect Agents Cancer 2018, 13 (1), 9. [DOI:10.1186/s13027-018-0180-y]
9. Nguyen, D.-H.; Chong, A.; Hong, Y.; Min, J.-J. Bioengineering of Bacteria for Cancer Immunotherapy. Nat Commun 2023, 14 (1), 3553. [DOI:10.1038/s41467-023-39224-8]
10. Lou, X.; Chen, Z.; He, Z.; Sun, M.; Sun, J. Bacteria-Mediated Synergistic Cancer Therapy: Small Microbiome Has a Big Hope. Nano-Micro Lett. 2021, 13 (1), 37. [DOI:10.1007/s40820-020-00560-9]
11. Badie, F.; Ghandali, M.; Tabatabaei, S. A.; Safari, M.; Khorshidi, A.; Shayestehpour, M.; Mahjoubin-Tehran, M.; Morshedi, K.; Jalili, A.; Tajiknia, V.; Hamblin, M. R.; Mirzaei, H. Use of Salmonella Bacteria in Cancer Therapy: Direct, Drug Delivery and Combination Approaches. Front. Oncol. 2021, 11, 624759. [DOI:10.3389/fonc.2021.624759]
12. Patyar, S.; Joshi, R.; Byrav, D. P.; Prakash, A.; Medhi, B.; Das, B. Bacteria in Cancer Therapy: A Novel Experimental Strategy. J Biomed Sci 2010, 17 (1), 21. [DOI:10.1186/1423-0127-17-21]
13. Cheong, I.; Huang, X.; Bettegowda, C.; Diaz, L. A.; Kinzler, K. W.; Zhou, S.; Vogelstein, B. A Bacterial Protein Enhances the Release and Efficacy of Liposomal Cancer Drugs. Science 2006, 314 (5803), 1308-1311. [DOI:10.1126/science.1130651]
14. Felgner, S.; Kocijancic, D.; Frahm, M.; Weiss, S. Bacteria in Cancer Therapy: Renaissance of an Old Concept. International Journal of Microbiology 2016, 2016, 1-14. [DOI:10.1155/2016/8451728]
15. Brockstedt, D. G.; Giedlin, M. A.; Leong, M. L.; Bahjat, K. S.; Gao, Y.; Luckett, W.; Liu, W.; Cook, D. N.; Portnoy, D. A.; Dubensky, T. W. Listeria -Based Cancer Vaccines That Segregate Immunogenicity from Toxicity. Proc. Natl. Acad. Sci. U.S.A. 2004, 101 (38), 13832-13837. [DOI:10.1073/pnas.0406035101]
16. Wood, L. M.; Paterson, Y. Attenuated Listeria Monocytogenes: A Powerful and Versatile Vector for the Future of Tumor Immunotherapy. Front. Cell. Infect. Microbiol. 2014, 4. [DOI:10.3389/fcimb.2014.00051]
17. Van Pijkeren, J. P.; Morrissey, D.; Monk, I. R.; Cronin, M.; Rajendran, S.; O'Sullivan, G. C.; Gahan, C. G. M.; Tangney, M. A Novel Listeria Monocytogenes -Based DNA Delivery System for Cancer Gene Therapy. Human Gene Therapy 2010, 21 (4), 405-416. [DOI:10.1089/hum.2009.022]
18. Ngo, N.; Choucair, K.; Creeden, J. F.; Qaqish, H.; Bhavsar, K.; Murphy, C.; Lian, K.; Albrethsen, M. T.; Stanbery, L.; Phinney, R. C.; Brunicardi, F. C.; Dworkin, L.; Nemunaitis, J. Bifidobacterium SPP : The Promising Trojan Horse in the Era of Precision Oncology. Future Oncol. 2019, 15 (33), 3861-3876. [DOI:10.2217/fon-2019-0374]
19. Wang, L.; Vuletic, I.; Deng, D.; Crielaard, W.; Xie, Z.; Zhou, K.; Zhang, J.; Sun, H.; Ren, Q.;Guo, C. Bifidobacterium Breve as a Delivery Vector of IL-24 Gene Therapy for Head and Neck Squamous Cell Carcinoma in Vivo. Gene Ther 2017, 24 (11), 699-705. [DOI:10.1038/gt.2017.74]
20. Wei, C.; Xun, A. Y.; Wei, X. X.; Yao, J.; Wang, J. Y.; Shi, R. Y.; Yang, G. H.; Li, Y. X.; Xu, Z. L.;Lai, M. G.; Zhang, R.; Wang, L.-S.; Zeng, W. S. Bifidobacteria Expressing Tumstatin Protein for Antitumor Therapy in Tumor-Bearing Mice. Technol Cancer Res Treat 2016, 15 (3), 498-508. [DOI:10.1177/1533034615581977]
21. Morales, A.; Eidinger, D.; Bruce, A. W. Intracavitary Bacillus Calmette-Guerin in the Treatment of Superficial Bladder Tumors. Journal of Urology 1976, 116 (2), 180-182. [DOI:10.1016/S0022-5347(17)58737-6]
22. Biot, C.; Rentsch, C. A.; Gsponer, J. R.; Birkhäuser, F. D.; Jusforgues-Saklani, H.; Lemaître, F.; Auriau, C.; Bachmann, A.; Bousso, P.; Demangel, C.; Peduto, L.; Thalmann, G. N.; Albert, M. L.Preexisting BCG-Specific T Cells Improve Intravesical Immunotherapy for Bladder Cancer. Sci. Transl. Med. 2012, 4 (137). [DOI:10.1126/scitranslmed.3003586]
23. Yan, S.; Gan, Y.; Xu, H.; Piao, H. Bacterial Carrier-Mediated Drug Delivery Systems: A Promising Strategy in Cancer Therapy. Front. Bioeng. Biotechnol. 2025, 12, 1526612. [DOI:10.3389/fbioe.2024.1526612]
24. Toso, J. F.; Gill, V. J.; Hwu, P.; Marincola, F. M.; Restifo, N. P.; Schwartzentruber, D. J.; Sherry,R. M.; Topalian, S. L.; Yang, J. C.; Stock, F.; Freezer, L. J.; Morton, K. E.; Seipp, C.; Haworth,L.; Mavroukakis, S.; White, D.; MacDonald, S.; Mao, J.; Sznol, M.; Rosenberg, S. A. Phase I Study of the Intravenous Administration of Attenuated Salmonella Typhimurium to Patients With Metastatic Melanoma. Journal of Clinical Oncology 2002, 20 (1), 142-152. [DOI:10.1200/JCO.2002.20.1.142]
25. Zheng, P.; Fan, M.; Liu, H.; Zhang, Y.; Dai, X.; Li, H.; Zhou, X.; Hu, S.; Yang, X.; Jin, Y.; Yu,N.; Guo, S.; Zhang, J.; Liang, X.-J.; Cheng, K.; Li, Z. Self-Propelled and Near-InfraredPhototaxic Photosynthetic Bacteria as Photothermal Agents for Hypoxia-Targeted Cancer Therapy. ACS Nano 2021, 15 (1), 1100-1110. [DOI:10.1021/acsnano.0c08068]
26. Yazawa, K.; Fujimori, M.; Amano, J.; Kano, Y.; Taniguchi, S. Bifidobacterium Longum as a Delivery System for Cancer Gene Therapy: Selective Localization and Growth in Hypoxic Tumors. Cancer Gene Ther 2000, 7 (2), 269-274. [DOI:10.1038/sj.cgt.7700122]
27. Nuyts, S.; Van Mellaert, L.; Theys, J.; Landuyt, W.; Lambin, P.; Anné, J. Clostridium Spores for Tumor-Specific Drug Delivery: Anti-Cancer Drugs 2002, 13 (2), 115-125. [DOI:10.1097/00001813-200202000-00002]
28. Brockstedt, D. G.; Le, D. T.; Hassan, R.; Murphy, A.; Grous, J.; Dubensky, T. W.; Jaffee, E. M. Clinical Experience with Live-Attenuated, Double-Deleted (LADD) Listeria Monocytogenes Targeting Mesothelin-Expressing Tumors. j. immunotherapy cancer 2013, 1 (S1), P203, 20511426-1-S1-P203. [DOI:10.1186/2051-1426-1-S1-P203]
29. Le, D. T.; Wang-Gillam, A.; Picozzi, V.; Greten, T. F.; Crocenzi, T.; Springett, G.; Morse, M.; Zeh, H.; Cohen, D.; Fine, R. L.; Onners, B.; Uram, J. N.; Laheru, D. A.; Lutz, E. R.; Solt, S.; Murphy, A. L.; Skoble, J.; Lemmens, E.; Grous, J.; Dubensky, T.; Brockstedt, D. G.; Jaffee, E.Safety and Survival With GVAX Pancreas Prime and Listeria Monocytogenes -Expressing Mesothelin (CRS-207) Boost Vaccines for Metastatic Pancreatic Cancer. Journal of Clinical Oncology 2015, 33 (12), 1325-1333. [DOI:10.1200/JCO.2014.57.4244]
30. Basu, P.; Mehta, A.; Jain, M.; Gupta, S.; Nagarkar, R. V.; John, S.; Petit, R. A Randomized Phase 2 Study of ADXS11-001 Listeria Monocy'togenes-Listeriolysin O Immunotherapy With or Without Cisplatin in Treatment of Advanced Cervical Cancer. International Journal of Gynecological Cancer 2018, 28 (4), 764-772. [DOI:10.1097/IGC.0000000000001235]
31. Hassan, R.; Alley, E.; Kindler, H.; Antonia, S.; Jahan, T.; Honarmand, S.; Nair, N.; Whiting, C. C.; Enstrom, A.; Lemmens, E.; Tsujikawa, T.; Kumar, S.; Choe, G.; Thomas, A.; McDougall, K.; Murphy, A. L.; Jaffee, E.; Coussens, L. M.; Brockstedt, D. G. Clinical Response of LiveAttenuated, Listeria Monocytogenes Expressing Mesothelin (CRS-207) with Chemotherapy in Patients with Malignant Pleural Mesothelioma. Clinical Cancer Research 2019, 25 (19), 5787- 5798. [DOI:10.1158/1078-0432.CCR-19-0070]
32. Huh, W. K.; Brady, W. E.; Fracasso, P. M.; Dizon, D. S.; Powell, M. A.; Monk, B. J.; Leath, C. A.; Landrum, L. M.; Tanner, E. J.; Crane, E. K.; Ueda, S.; McHale, M. T.; Aghajanian, C. Phase II Study of Axalimogene Filolisbac (ADXS-HPV) for Platinum-Refractory Cervical Carcinoma: An NRG Oncology/Gynecologic Oncology Group Study. Gynecologic Oncology 2020, 158 (3), 562-569. [DOI:10.1016/j.ygyno.2020.06.493]
33. Tomita, Y.; Ikeda, T.; Sakata, S.; Saruwatari, K.; Sato, R.; Iyama, S.; Jodai, T.; Akaike, K.; Ishizuka, S.; Saeki, S.; Sakagami, T. Association of Probiotic Clostridium Butyricum Therapy with Survival and Response to Immune Checkpoint Blockade in Patients with Lung Cancer. Cancer Immunology Research 2020, 8 (10), 1236-1242. [DOI:10.1158/2326-6066.CIR-20-0051]
34. Stein, M. N.; Fong, L.; Tutrone, R.; Mega, A.; Lam, E. T.; Parsi, M.; Vangala, S.; Gutierrez, A. A.; Haas, N. B. ADXS31142 Immunotherapy ± Pembrolizumab Treatment for Metastatic Castration-Resistant Prostate Cancer: Open-Label Phase I/II KEYNOTE-046 Study. The Oncologist 2022, 27 (6), 453-461. [DOI:10.1093/oncolo/oyac048]
35. Dizman, N.; Meza, L.; Bergerot, P.; Alcantara, M.; Dorff, T.; Lyou, Y.; Frankel, P.; Cui, Y.; Mira, V.; Llamas, M.; Hsu, J.; Zengin, Z.; Salgia, N.; Salgia, S.; Malhotra, J.; Chawla, N.; ChehraziRaffle, A.; Muddasani, R.; Gillece, J.; Reining, L.; Trent, J.; Takahashi, M.; Oka, K.; Higashi, S.; Kortylewski, M.; Highlander, S. K.; Pal, S. K. Nivolumab plus Ipilimumab with or without Live Bacterial Supplementation in Metastatic Renal Cell Carcinoma: A Randomized Phase 1 Trial. Nature Medicine 2022, 28 (4), 704-712. [DOI:10.1038/s41591-022-01694-6]
36. Ebrahimi, H.; Dizman, N.; Meza, L.; Malhotra, J.; Li, X.; Dorff, T.; Frankel, P.; Llamas-Quitiquit,M.; Hsu, J.; Zengin, Z. B.; Alcantara, M.; Castro, D.; Mercier, B.; Chawla, N.; Chehrazi-Raffle, A.; Barragan-Carrillo, R.; Jaime-Casas, S.; Govindarajan, A.; Gillece, J.; Trent, J.; Lee, P. P.;Parks, T. P.; Takahashi, M.; Hayashi, A.; Kortylewski, M.; Caporaso, J. G.; Lee, K.; Tripathi, A.;Pal, S. K. Cabozantinib and Nivolumab with or without Live Bacterial Supplementation in Metastatic Renal Cell Carcinoma: A Randomized Phase 1 Trial. Nature Medicine 2024, 30 (9), 2576-2585. [DOI:10.1038/s41591-024-03086-4]
37. Sivan, A.; Corrales, L.; Hubert, N.; Williams, J. B.; Aquino-Michaels, K.; Earley, Z. M.; Benyamin, F. W.; Man Lei, Y.; Jabri, B.; Alegre, M.-L.; Chang, E. B.; Gajewski, T. F. Commensal Bifidobacterium Promotes Antitumor Immunity and Facilitates Anti-PD-L1 Efficacy. Science 2015, 350 (6264), 1084-1089. [DOI:10.1126/science.aac4255]
38. Shi, L.; Sheng, J.; Wang, M.; Luo, H.; Zhu, J.; Zhang, B.; Liu, Z.; Yang, X. Combination Therapy of TGF-β Blockade and Commensal-Derived Probiotics Provides Enhanced Antitumor Immune Response and Tumor Suppression. Theranostics 2019, 9 (14), 4115-4129. [DOI:10.7150/thno.35131]
39. León-Letelier, R. A.; Castro-Medina, D. I.; Badillo-Godinez, O.; Tepale-Segura, A.; HuanostaMurillo, E.; Aguilar-Flores, C.; De León-Rodríguez, S. G.; Mantilla, A.; Fuentes-Pananá, E. M.; López-Macías, C.; Bonifaz, L. C. Induction of Progenitor Exhausted Tissue-Resident Memory CD8+ T Cells Upon Salmonella Typhi Porins Adjuvant Immunization Correlates With Melanoma Control and Anti-PD-1 Immunotherapy Cooperation. Front. Immunol. 2020, 11, 583382. [DOI:10.3389/fimmu.2020.583382]
40. Yi, X.; Zhou, H.; Chao, Y.; Xiong, S.; Zhong, J.; Chai, Z.; Yang, K.; Liu, Z. Bacteria-Triggered Tumor-Specific Thrombosis to Enable Potent Photothermal Immunotherapy of Cancer. Sci. Adv. 2020, 6 (33), eaba3546. [DOI:10.1126/sciadv.aba3546]
41. Liu, X.; Wu, M.; Wang, M.; Duan, Y.; Phan, C.; Qi, G.; Tang, G.; Liu, B. Metabolically Engineered Bacteria as Light-Controlled Living Therapeutics for Anti-Angiogenesis Tumor Therapy. Mater. Horiz. 2021, 8 (5), 1454-1460. [DOI:10.1039/D0MH01582B]
42. Xu, W.; Ren, D.; Yu, Z.; Hou, J.; Huang, F.; Gan, T.; Ji, P.; Zhang, C.; Ma, L.; Hu, Y. BacteriaMediated Tumor Immunotherapy via Photothermally-Programmed PD1 Expression. Nanoscale Adv. 2022, 4 (6), 1577-1586. [DOI:10.1039/D1NA00857A]
43. Sun, R.; Liu, M.; Lu, J.; Chu, B.; Yang, Y.; Song, B.; Wang, H.; He, Y. Bacteria Loaded with Glucose Polymer and Photosensitive ICG Silicon-Nanoparticles for Glioblastoma Photothermal Immunotherapy. Nat Commun 2022, 13 (1), 5127. [DOI:10.1038/s41467-022-32837-5]
44. Moreo, E.; Uranga, S.; Picó, A.; Gómez, A. B.; Nardelli-Haefliger, D.; Del Fresno, C.; Murillo,I.; Puentes, E.; Rodríguez, E.; Vales-Gómez, M.; Pardo, J.; Sancho, D.; Martín, C.; Aguilo, N. Novel Intravesical Bacterial Immunotherapy Induces Rejection of BCG-Unresponsive Established Bladder Tumors. J Immunother Cancer 2022, 10 (7), e004325. [DOI:10.1136/jitc-2021-004325]
45. Howard, F. H. N.; Al‐Janabi, H.; Patel, P.; Cox, K.; Smith, E.; Vadakekolathu, J.; Pockley, A. G.; Conner, J.; Nohl, J. F.; Allwood, D. A.; Collado‐Rojas, C.; Kennerley, A.; Staniland, S.; Muthana, Nanobugs as Drugs: Bacterial Derived Nanomagnets Enhance Tumor Targeting and Oncolytic Activity of HSV‐1 Virus. Small 2022, 18 (13), 2104763. [DOI:10.1002/smll.202104763]
46. Xu, H.; Piao, L.; Wu, Y.; Liu, X. IFN-γ Enhances the Antitumor Activity of Attenuated Salmonella-Mediated Cancer Immunotherapy by Increasing M1 Macrophage and CD4 and CD8 T Cell Counts and Decreasing Neutrophil Counts. Front. Bioeng. Biotechnol. 2022, 10, 996055. [DOI:10.3389/fbioe.2022.996055]
47. Shi, L.; Liu, X.; Li, Y.; Li, S.; Wu, W.; Gao, X.; Liu, B. Living Bacteria‐Based ImmunoPhotodynamic Therapy: Metabolic Labeling of Clostridium Butyricum for Eradicating Malignant Melanoma. Advanced Science 2022, 9 (14), 2105807. [DOI:10.1002/advs.202105807]
48. Ijaz, M.; Hasan, I.; Chaudhry, T. H.; Huang, R.; Zhang, L.; Hu, Z.; Tan, Q.; Guo, B. Bacterial Derivatives Mediated Drug Delivery in Cancer Therapy: A New Generation Strategy. J Nanobiotechnol 2024, 22 (1), 510. [DOI:10.1186/s12951-024-02786-w]
49. Gholami, A.; Mohkam, M.; Soleimanian, S.; Sadraeian, M.; Lauto, A. Bacterial Nanotechnology as a Paradigm in Targeted Cancer Therapeutic Delivery and Immunotherapy. Microsyst Nanoeng 2024, 10 (1), 113.
https://doi.org/10.1038/s41378-024-00743-z [DOI:10.1038/s41378-024-00743-z.]
Send email to the article author
| Rights and permissions | |
 |
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
- Iranian Journal of Blood and Cancer
- Journal Tel: +989369936116
- Publisher Tel: +982122275917
- Mail: Info@ijbc.ir
