Can engineered bacteria help control cancer?

Jain, Rakesh K.; Forbes, Neil S.

doi:10.1073/pnas.261606598

Cited by 98 publications

(73 citation statements)

References 22 publications

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“…The rationale behind this combined therapy (called combination bacteriolytic therapy, or COBALT) was that the anaerobic bacteria grew in the anaerobic zone within tumor cores; the anti-vascular agent would create more extensive hypoxic areas for bacterial growth, thereby depriving the tumors of oxygen and essential nutrients while the chemotherapeutic agent attacked and destroyed the remaining well-perfused tumor cells. 8 The results of this study were highly significant: in the absence of bacteria, but in the presence of mitomycin C and dolastatin -10, the tumors persisted for a much longer time and showed limited regression, while inclusion of bacteria led to extensive disappearance of the tumors within a short period of time and, in some cases, complete tumor dissolution that left the animal tumor-free. The major limitation of this study was its associated toxicity: 15-45% of the mice died within few days of beginning treatment, presumably due to the release of highly toxic metabolic products from the disintegrating tumors.…”

Section: Introductionmentioning

confidence: 72%

Microbial based therapy of cancer: A new twist to an age old practice

Punj

Saint‐Dic²,

Daghfal³

et al. 2004

Cancer Biology & Therapy

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The use of bacteria in the regression of tumors has long been known. Various approaches for using bacteria in cancer therapy include the use of bacteria as sensitizing agents for chemotherapy, as delivery agents for cancer drugs and as agents for gene therapy. The tumor regression stimulated by infecting microorganisms has been attributed to activation of the immune system of the host. However, recent studies indicate that when tumorharboring mice with defective immune systems are infected with certain microorganisms, the regression of the tumor is still observed, suggesting that there are other host factors contributing to the microbial associated regression of tumors. Since the use of live or attenuated bacteria for tumor regression has associated toxic effects, studies are in progress to identify a pure microbial metabolite or any component of the microbial cell that might have anti-cancer activity. It has now been demonstrated that a redox protein from Pseudomonas aeruginosa, a cupredoxin, can enter into human cancer cells and trigger the apoptotic cell death. In vivo, this cupredoxin can lead to the regression of tumor growth in immunodeficient mice harboring xenografted melanomas and breast cancer tumors without inducing significant toxic effects, suggesting that it has potential anti-cancer activity. This bacterial protein interacts with p53 and modulates mammalian cellular activity. Hence, it could potentially be used as an anti-cancer agent for solid tumors and has translational value in tumor-targeted or in combinational-biochemotherapy strategies for cancer treatments. Here, we focus on diverse approaches to cancer biotherapy, including bacteriolytic and bacterially-derived anti-cancer agents with an emphasis on their mechanism of action and therapeutic potential.

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Section: Introductionmentioning

confidence: 72%

Microbial based therapy of cancer: A new twist to an age old practice

Punj

Saint‐Dic²,

Daghfal³

et al. 2004

Cancer Biology & Therapy

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“…Such microbe-host protein-carbohydrate interaction (Karlsson, 2001) is not only the essential step to produce infection, but also it leads to a status alternation of the host cells, for instance, the induction of apoptosis (Mulvey et al, 1998;Klumpp et al, 2006). Engineered bacteria are able to help control cancer (Jain and Forbes, 2001). PA-MSHA is a genetically established, engineered Pseudomonas aeruginosa (PA) strain characterized by the expression of mannosesensitive type 1 fimbriae on its surface.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of EGFR pathway signaling and the metastatic potential of breast cancer cells by PA-MSHA mediated by type 1 fimbriae via a mannose-dependent manner

Liu

Hou

Zhu³

et al. 2010

Oncogene

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To identify more therapeutic targets and clarify the detailed mechanisms of Pseudomonas aeruginosa-mannosesensitive hemagglutinin (PA-MSHA) on breast cancer cells both in vitro and in vivo. PA-MSHA was administered to epidermal growth factor receptor (EGFR)-positive human breast cancer cell lines MDA-MB-231HM and MDA-MB-468 in vitro and to mice bearing tumor xenografts. The mannose cocultured test was used to detect the effect of mannose on PA-MSHA-induced cell proliferation, cell cycle arrest, apoptosis, and EGFR pathway signaling. We found that cells stimulated with PA-MSHA exhibited a downregulation of EGFR signaling. The addition of mannose partially inhibited the PA-MSHA-stimulated cell anti-proliferative effect, cell apoptosis, cell cycle arrest, activation of apoptosis-associated caspases, and even downregulation of the EGFR signaling pathway. In vivo, PA-MSHA treatment significantly suppressed mammary tumorigenesis in xenografts in mice and decreased lung metastasis in MDA-MB-231HM celltransplanted mice. Tumor sample analyses confirmed inhibition of the EGFR pathway in the PA-MSHAtreated mice. In conclusion, this study showed that the involvement of the mannose-mediated EGFR pathway has a critical function in the preclinical rationale for the development of PA-MSHA for the treatment of human breast cancer. It also suggests the potentially beneficial use of PA-MSHA in adjuvant therapy for breast tumors with EGFR overexpression.

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“…This provides new options for amelioration of metabolic disorders, allergies or autoimmune diseases [2,[8][9][10] but also for delivery of anticancer drugs and detection of residual cancerous tissue [11][12][13].…”

Section: Introductionmentioning

confidence: 99%