Cytotoxicity and reduction of animal cell growth by clostridium M-55 spores and their extracts

Chagnon, A.; Hudon, Christiane; McSween, G.; Vinet, Guy; Fredette, V.

doi:10.1002/1097-0142(197202)29:2<431::aid-cncr2820290226>3.0.co;2-z

Cited by 13 publications

(5 citation statements)

References 5 publications

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“…During infection by Clostridium spp., a variety of secreted bacterial toxins (such as hemolysins and phospholipases) can perturb cellular membrane structure or interfere with intracellular functions 24,42,43 . Like Salmonella and Listeria spp.…”

Section: Mechanisms By Which Bacteria Target and Suppress Tumorsmentioning

confidence: 99%

Bacteria-cancer interactions: bacteria-based cancer therapy

et al. 2019

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Recent advances in cancer therapeutics, such as targeted therapy and immunotherapy, have raised the hope for cures for many cancer types. However, there are still ongoing challenges to the pursuit of novel therapeutic approaches, including high toxicity to normal tissue and cells, difficulties in treating deep tumor tissue, and the possibility of drug resistance in tumor cells. The use of live tumor-targeting bacteria provides a unique therapeutic option that meets these challenges. Compared with most other therapeutics, tumor-targeting bacteria have versatile capabilities for suppressing cancer. Bacteria preferentially accumulate and proliferate within tumors, where they can initiate antitumor immune responses. Bacteria can be further programmed via simple genetic manipulation or sophisticated synthetic bioengineering to produce and deliver anticancer agents based on clinical needs. Therapeutic approaches using live tumor-targeting bacteria can be applied either as a monotherapy or in combination with other anticancer therapies to achieve better clinical outcomes. In this review, we introduce and summarize the potential benefits and challenges of this anticancer approach. We further discuss how live bacteria interact with tumor microenvironments to induce tumor regression. We also provide examples of different methods for engineering bacteria to improve efficacy and safety. Finally, we introduce past and ongoing clinical trials involving tumor-targeting bacteria.

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Section: Mechanisms By Which Bacteria Target and Suppress Tumorsmentioning

confidence: 99%

Bacteria-cancer interactions: bacteria-based cancer therapy

et al. 2019

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“…Fredette and coworkers gave an account of a cytotoxic factor released from germinating Clostridium oncolyticum spores which selectively inhibited transplantable heteroploid cell lines in distinct proportions of spores to eukaryotic cells, while diploid cell lines remained unchanged (28,29). Similar effects were observed by Schlechte et al (30).…”

Section: Experimental Approach To Clostridial Oncolysismentioning

confidence: 70%

The tumour-Clostridium phenomenon: 50 years of developmental research (Review)

Schmidt

Fabricius²,

Schneeweiss³

2006

Int J Oncol

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Abstract. The tumour-Clostridium phenomenon describes the specific affinity of spore forming anaerobes to tumour growth. The discovery of strictly intratumoral tetanus toxicoinfections in tumour-bearing mice after intravenous spore administration gave the impulse to search for non-toxic clostridial isolates with tumour-selective properties for clostridial biotherapy, i.e. oncolysis, as well as serologic tumour diagnostics without any toxic side-effects. Systematic studies of the oncolytic process and its variables on diverse experimental tumours and laboratory animals revealed that tumour liquefaction, converting necrotic tumour parts to putrid abscesses filled with masses of clostridial forms, stops sharply at the viable rim of the blood-supplied tumour tissue. Similar results were observed in clinical trials, particular of gliomas. Before oncolysis is initiated, the first stage of clostridial multiplication in the vascularized tissue is inducing a humoural immune response, preceded by phagocytic activity. The majority of tumour-bearing laboratory and domestic animals, so far tested serologically, clinical cancer patients as well, responded with anti-rod antibodies and, independently, antispore antibodies. Oncolytic and non-oncolytic Clostridia were equally immunogenic. During the early, immunizing period of clostridial proliferation, analytical tumour-tetanus experiments were focused on potential relations between tumour growth kinetics and rod proliferation. Based on realistic growth models and target principles, computer simulations could reproduce the results, i.e. cumulative curves of tetanus lethality in groups of mice. Thus, crucial assumptions of the mathematical model were ex post confirmed by further experiments. Our working hypothesis concentrates on temporally hypoxic micro-niches close to a pre-mitotic cell with enhanced oxygen demand which can be utilized by anaerobes (randomly) located there. As early immune reactions to clostridial antigens via phagocytosis and humoural immune response will do without invasion in necrobiotic avascular tumour areas, the pacemaker model of tumour-Clostridium interplay extends the scope of genetically engineered Clostridia to early treatment of metastases. Thus, novel concepts, such as 'Clostridia-directed enzyme prodrugtherapy' and 'Combined bacteriolytic therapy', together with immune activation, can come into play.

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“…( 17 ) Direct tumor destruction is caused by a variety of exotoxins secreted by the colonizing clostridia, some of which (e.g. phospholipases, haemolysins, lipases) can damage membrane structures while others are internalized to interfere with critical cellular functions 204-207 . ( 18 ) Similar to infection by other bacterial species, the clostridial infection results in an initial accumulation of granulocytes and macrophages at the infection site 47,55 .…”

Section: Figmentioning

confidence: 99%

Tumour-targeting bacteria engineered to fight cancer

et al. 2018

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Recent advances in targeted therapy and immunotherapy have once again raised the hope that a cure might be within reach for many cancer types. Yet, the majority of cancers are either insensitive to the therapies to begin with or develop resistance later on. Therapy with live tumor-targeting bacteria provides a unique option to meet these challenges. Compared to most other therapeutics, the effectiveness of tumor-targeting bacteria is not directly affected by the genetic makeup of a tumor. Bacteria initiate their direct antitumor effects from deep within the tumor, followed by innate and adaptive antitumor immune responses. As microscopic “robotic factories”, bacterial vectors can be reprogrammed following simple genetic rules or sophisticated synthetic bioengineering principles to produce and deliver anticancer agents based on clinical needs. Therapeutic approaches using live tumor-targeting bacteria can either be applied as a monotherapy or complement other anticancer therapies to achieve better clinical outcomes. In this Review, we summarize the potential benefits and challenges of this approach. We discuss how live bacteria selectively induce tumor regression and provide examples to illustrate different ways to engineer bacteria for improved safety and efficacy. Finally, we share our experience and insights on oncology clinical trials with tumor-targeting bacteria, including a discussion on regulatory issues.

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Cytotoxicity and reduction of animal cell growth by clostridium M-55 spores and their extracts

Cited by 13 publications

References 5 publications

Bacteria-cancer interactions: bacteria-based cancer therapy

Bacteria-cancer interactions: bacteria-based cancer therapy

The tumour-Clostridium phenomenon: 50 years of developmental research (Review)

Tumour-targeting bacteria engineered to fight cancer

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