Use of Bacteria in Cancer Therapy

Sarotra, Pooja; Medhi, Bikash

doi:10.1007/978-3-319-42934-2_8

Cited by 32 publications

(18 citation statements)

References 14 publications

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“…The prognosis of TNBC patients remains poor due to the lack of effective targeted therapies and the recurrent and aggressive nature of the disease. There is a burgeoning interest in utilizing the properties of bacteria [36,37,38], bacterial products [39], and oncolytic viruses [40,41,42] to develop novel approaches to cancer therapy. Microbial products were at the forefront of cancer therapy as early as the 1890s, with the advent of the immune stimulating Coley’s Toxins.…”

Section: Discussionmentioning

confidence: 99%

“…Microbial products were at the forefront of cancer therapy as early as the 1890s, with the advent of the immune stimulating Coley’s Toxins. In addition to immune stimulation, direct mechanisms to target cancer are under investigation [3,36,43]. A number of microorganisms and their products have been shown to perturb the autophagic pathway [44,45].…”

Section: Discussionmentioning

confidence: 99%

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LT-IIc, A Bacterial Type II Heat-Labile Enterotoxin, Induces Specific Lethality in Triple Negative Breast Cancer Cells by Modulation of Autophagy and Induction of Apoptosis and Necroptosis

Masso-Welch

Berlingeri

King-Lyons

et al. 2018

IJMS

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Triple negative breast cancer (TNBC) remains a serious health problem with poor prognosis and limited therapeutic options. To discover novel approaches to treat TNBC, we screened cholera toxin (CT) and the members of the bacterial type II heat-labile enterotoxin family (LT-IIa, LT-IIb, and LT-IIc) for cytotoxicity in TNBC cells. Only LT-IIc significantly reduced viability of the TNBC cell lines BT549 and MDA-MB-231 (IC50 = 82.32 nM). LT-IIc had no significant cytotoxic effect on MCF10A (IC50 = 2600 nM), a non-tumorigenic breast epithelial cell line, and minimal effects on MCF7 and T47D, ER+ cells, or SKBR-3 cells, HER2+ cells. LT-IIc stimulated autophagy through inhibition of the mTOR pathway, while simultaneously inhibiting autophagic progression, as seen by accumulation of LC3B-II and p62. Morphologically, LT-IIc induced the formation of enlarged LAMP2+ autolysosomes, which was blocked by co-treatment with bafilomycin A1. LT-IIc induced apoptosis as demonstrated by the increase in caspase 3/7 activity and Annexin V staining. Co-treatment with necrostatin-1, however, demonstrated that the lethal response of LT-IIc is elicited, in part, by concomitant induction of necroptosis. Knockdown of ATG-5 failed to rescue LT-IIc-induced cytotoxicity, suggesting LT-IIc can exert its cytotoxic effects downstream or independently of autophagophore initiation. Collectively, these experiments demonstrate that LT-IIc acts bifunctionally, inducing autophagy, while simultaneously blocking autolysosomal progression in TNBC cells, inducing a specific cytotoxicity in this breast cancer subtype.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

LT-IIc, A Bacterial Type II Heat-Labile Enterotoxin, Induces Specific Lethality in Triple Negative Breast Cancer Cells by Modulation of Autophagy and Induction of Apoptosis and Necroptosis

Masso-Welch

Berlingeri

King-Lyons

et al. 2018

IJMS

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“…The late stage of cancer that is sensitive to the conventional therapies becomes resistant later. Cancer vaccines and biological therapies are helpful to tumor cells in addition to conventional therapies, because they are characterized by less toxicity and specific targeting of tumor cells [ 115 ].…”

Section: Bacteria In Cancer Therapymentioning

confidence: 99%

Dual Role of Bacteria in Carcinoma: Stimulation and Inhibition

Al-Hilu

Al-Shujairi

2020

International Journal of Microbiology

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Although what unifies the carcinogenic microorganisms has not been determined by multiple studies, the role of bacteria in the development of neoplasms has not been properly elucidated. In this review, we discuss links between the bacterial species and cancer, with focus on immune responses for the stimulation of tumor cells such as induction of inflammation. Finally, we will describe the potential therapeutic strategies of bacteria on target tumors to improve treatment while mitigating adverse reactions. Cancer is a series of genetic changes that transform normal cells into tumor cells. These changes come from several reasons, including smoking, drinking alcohol, sunlight, exposure to chemical or physical factors, and finally chronic infection with microorganisms, including bacteria. In fact, bacterial infections are not carcinogenic, but recently it was discovered that the association between bacteria and cancer is through two mechanisms, the first stimulating chronic inflammation and the second producing carcinogenic metabolites. While bacteria are carcinogenic agents also, they have a dual role eliminating and removing tumor cells. However, the traditional cancer treatments that include chemotherapy, radiotherapy, surgery, and immunotherapy increase the chances of survival, and there are many side effects of these therapies, including the high toxicity of tissues and normal cells, could not penetrate the tumor cells, and resistance of these therapies by tumor cells. Therefore, the world has turned to an alternative solution, which is the use of genetically engineered microorganisms; thus, the use of living bacteria targeting cancerous cells is the unique option to overcome these challenges. Bacterial therapies, whether used alone or combination with chemotherapy, give a positive effect to treat multiple conditions of cancer. Also, bacteria can be used as vectors for drug, gene, or therapy, and this is a great step to treat cancer. Thus, we review the mechanisms underlying the interaction of the microbiota residents with cancer. Cancer-associated bacteria differ from those in healthy human and are linked with gene-expression profile. We also discuss how live bacteria interact with tumor microenvironments to induce tumor regression through colonization and spread. Finally, we provide past and ongoing clinical trials that include bacteria targeting tumors.

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“…and Listeria sp. was further explored by many investigators [15]. An advantage of bacteria-based therapy is high tumor specificity.…”

Section: Oncolytic Pathogen-based Therapymentioning

confidence: 99%

Two is Better Than One: Advances in Pathogen-Boosted Immunotherapy and Adoptive T-Cell Therapy

Schauder

Zander

et al. 2017

Immunotherapy

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The recent tremendous successes in clinical trials take cancer immunotherapy into a new era and have attracted major attention from both academia and industry. Among the variety of immunotherapy strategies developed to boost patients' own immune systems to fight against malignant cells, the pathogen-based and adoptive cell transfer therapies have shown the most promise for treating multiple types of cancer. Pathogen-based therapies could either break the immune tolerance to enhance the effectiveness of cancer vaccines or directly infect and kill cancer cells. Adoptive cell transfer can induce a strong durable antitumor response, with recent advances including engineering dual specificity into T cells to recognize multiple antigens and improving the metabolic fitness of transferred cells. In this review, we focus on the recent prospects in these two areas and summarize some ongoing studies that represent potential advancements for anticancer immunotherapy, including testing combinations of these two strategies.

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Use of Bacteria in Cancer Therapy

Cited by 32 publications

References 14 publications

LT-IIc, A Bacterial Type II Heat-Labile Enterotoxin, Induces Specific Lethality in Triple Negative Breast Cancer Cells by Modulation of Autophagy and Induction of Apoptosis and Necroptosis

LT-IIc, A Bacterial Type II Heat-Labile Enterotoxin, Induces Specific Lethality in Triple Negative Breast Cancer Cells by Modulation of Autophagy and Induction of Apoptosis and Necroptosis

Dual Role of Bacteria in Carcinoma: Stimulation and Inhibition

Two is Better Than One: Advances in Pathogen-Boosted Immunotherapy and Adoptive T-Cell Therapy

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