Corresponding Author:Mohamed Imath*1 Mohan Raj1, Saraswati Patel1, Sathyanathan Viswanathan1 Apollo College of Pharmacy, Kanchipuram, Chennai. Department of Pharmacology Mohamedimath786@gmail.com

1. Bacteriotherapy in cancer their roles and
bottlenecks: The systematic review
Corresponding Author:Mohamed Imath*1
Mohan Raj1, Saraswati Patel1,
Sathyanathan Viswanathan1
Apollo College of Pharmacy, Kanchipuram, Chennai. Department of Pharmacology
Mohamedimath786@gmail.com
International Conference on Advanced Innovation and
Research Challenges in Science & Technology-
ICAIRST 2023

2. Abstract
• Successful treatment of cancer remains a challenge, due to the unique
pathophysiology of solid tumours, and the predictable emergence of
resistance. Traditional methods for cancer therapy including radiotherapy,
chemotherapy, and immunotherapy all have their own limitations. A novel
approach is bacteriotherapy, either used alone, or in combination with
conventional methods, has shown a positive effect on regression of tumours
and inhibition of metastasis. Bacteria‐assisted tumour‐targeted therapy used
as therapeutic/gene/drug delivery vehicles has great promise in the treatment
of tumours. The use of bacteria only, or in combination with conventional
methods was found to be effective in some experimental models of cancer
(tumour regression and increased survival rate). In this article, I reviewed the
strategies, clinical trials, role of bacteria in cancer cells and future
prospective for bacteria based tumour therapy.
• Keywords: bacteriotherapy, cancer, strategies, role, clinical trials.

3. Introduction:
• Cancer remains one of the most common causes of death throughout the
world. These statistics emphasize the urgency of finding novel and more
effective treatments. The historical treatment options for cancer, including
surgery, radiotherapy, chemotherapy, and immunotherapy all have some
limitations. Nowadays, Alternative or complementary therapies such as gene
therapy, diet therapy, photodynamic therapy, insulin potentiating therapy,
HAMLET (human alpha‐lactalbumin made lethal to tumor cells), telomerase
therapy, hyperthermia therapy, dichloroacetate, non‐invasive RF cancer
treatment, and bacteriotherapy have been proposed to improve and increase
the effectiveness of conventional cancer therapy.

4. Hypothesis
The use of therapeutic bacteria is one approach that may be able to overcome
some of the limitations of conventional cancer therapy as stated above. Bacteria
alone can act as potent antitumor agents. Another remarkable feature of bacteria
is their ability to be genetically engineered to alter their ability to synthesize and
release specific compounds, and tailor their metabolic pathways.

5. Role of bacteria in Cancerous cell

6. Bacteria in cancer therapy:
• Cancer is a challenging disease, which requires a multi‐pronged approach for
effective treatment. For the first time clinicians used live bacteria
(Streptococci and Clostridia) for cancer treatment.
• Today, genetically modified bacteria are mostly used for this purpose.
• The most common bacteria used in this field are the
genera Salmonella, Clostridium, Bifidobacterium, Lactobacillus, Escherichia, P
seudomonas, Caulobacter, Listeria, Proteus, and Streptococcus.
• The use of three species of bacteria, Clostridia, Bifidobacteria,
and Salmonellae as vectors for delivering or expressing tumor suppressor genes,
anti‐angiogenic genes, suicide genes, or tumor‐associated antigens has been
tested in animal models bearing various tumors.

7. The treatment strategy of bacteria in cancer therapy
Treatment strategy Type of bacteria, treatment
approach
Outcome
Immunotherapeutic agents Streptococcus pyogenes,
intentionally infected a cancer
patient with erysipelas
Rapid tumor regression
Immunotherapeutic agents Bacillus Calmette‐Guerin,
injection into patients with
tuberculosis
Reduced frequency of cancer
Immunotherapeutic agents Clostridium spp, concurrently
suffered from gas gangrene in
patients with tumor
Tumor regression
Immunotherapeutic agents Attenuated Salmonella
typhimurium, vaccination of
the B16F10 tumor‐bearing
mice by
derivatives Salmonella
typhimurium
An antitumor effect

8. Treatment strategy Type of bacteria, treatment
approach
Outcome
Vectors/spores to carry
tumoricidal agents
Clostridium novyi‐NT, IV
injection of C novyi‐NT
spores and a single IV dose of
liposomal doxorubicin (Doxil)
administered into mice
bearing colorectal cancer
Elimination of tumors
Vectors/spores to carry
tumoricidal agents
C novyi‐NT, IV administration
of HTI‐286, docetaxel,
vinorelbime, and MAC‐321 in
combination with or without C
novyi‐NT spores into mice
bearing HTC 116 xenografts
Hemorrhagic necrosis of
tumors
Vectors/spores to carry
tumoricidal agents
C novyi‐NT spores, IV
injection C novyi‐NT spores
into CT26 and RENCA tumors
in mice and VX2 tumor in
rabbits
Relatively treated in mice and
rabbits with cancer
Cont.

9. Clinical Trials
Bacterial strain Trial phase Cancer type
Clostridium novyi-NT I Colorectal cancer
Leiomyosarcoma
Solid tumor malignancies
Listeria monocytogenes III Cervical cancer
II Metastatic pancreatic tumors
Salmonella
typhimurium VNP20009
I Metastatic renal cell carcinoma
and metastatic melanoma
S. typhimurium expressing
human IL-2
I Liver cancer
S. typhimurium Ty21a VXM01 I Pancreatic cancer

10. Genetically modified bacteria in cancer therapy:
• Gene therapy is a forward‐looking alternative approach to cancer therapy.
Selective targeting and destruction of tumor cells are the major advantages of
gene therapy. Genetically modified bacteria may also be able to lower
pathogenicity to the host and increase the antitumor efficacy. Recently, a
number of studies have developed a new approach for cancer therapy using
genetically engineered bacteria designed to express reporter genes, cytotoxic
protein and/or anticancer agents, and tumor‐specific antigens

11. Future prospective
• Bacteria-based cancer therapy has great potential to address the gaps in past
failures, such as the complexity of tumor bacteria interactions, so the field
remains challenging to researchers. The past obstacles can be overcome by the
use of genetically modified microorganisms and sophisticated genetic
engineering technology, which may have great applications in cancer therapy. In
the future, bacterial combinations can be used to enhance the efficacy of
immunotherapy, chemotherapy and radiotherapy.
Conclusion:
• The advanced knowledge of bacterial pathogenesis, immunology and cancer
biology provides a better understanding of bacteria-based cancer therapy.
Genetic manipulation and new molecular technologies have made it possible to
revisit bacteria-based cancer therapy from a future perspective.

12. Acknowledgement:
• We thank Mr. E.Thendral Arasu and Mr. K.Mohan Raj for their
helpful discussion. Our work was supported by Dr. Saraswati
Patel M.Pharm., Ph.D., Assistant Professor and Dr. V.
Sathyanathan M.Pharm., Ph.D., (Principal). Then great thanks
to Apollo College of Pharmacy, Chennai.
References:
1. Cheadle, E. J., and Jackson, A. M. (2002). Bugs as drugs for
cancer. Immunology 107, 10–19. doi: 10.1046/j.1365-2567.2002.01498.x
2. Gahan, M. E., Webster, D. E., Wesselingh, S. L., Strugnell, R. A., and Yang, J.
(2009). Bacterial antigen expression is an important component in inducing an
immune response to orally administered Salmonella-delivered DNA
vaccines. PLOS ONE 4:e6062. doi: 10.1371/journal.pone.0006062
3. Forbes, N. S. (2010). Engineering the perfect (bacterial) cancer therapy. Nat.
Rev. Cancer 10, 785–794. doi: 10.1038/nrc2934
4. Fink, S. L., and Cookson, B. T. (2007). Pyroptosis and host cell death responses
during Salmonella infection. Cell. Microbiol. 9, 2562–2570. doi: 10.1111/j.1462-
5822.2007.01036.x
5. Hoffman, R. M. (ed.) (2016c). “Future of bacterial therapy of cancer,”
in Methods in Molecular Biology, (New York, NY: Humana Press), 177–184.
doi: 10.1007/978-1-4939-3515-4_15

13. THANK YOU