Bacteria in cancer therapy: a novel experimental strategy

Patyar, Sazal; Joshi, Rupa; Byrav, DS Prasad; Prakash, Ajay; Medhi, Bikash; Das, Bikash

doi:10.1186/1423-0127-17-21

Cited by 280 publications

(235 citation statements)

References 47 publications

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“…This method has drawn further attention with the development of techniques to genetically modify the bacteria, thereby enabling the expression of anti-cancer therapeutic genes in these hosts. 26 Numerous publications provide convincing evidence that genera of bacteria including Bifidobacterium and commensal Escherichia coli have potential in cancer therapy. 9,10,12,16,[27][28][29][30] This vector class compares favorably with other vectors in terms of key attributes such as safety, ease of manipulation, and production.…”

Section: Bacterial-mediated Tumor Therapymentioning

confidence: 99%

Bacterial vectors for imaging and cancer gene therapy: a review

et al. 2012

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The significant burden of resistance to conventional anticancer treatments in patients with advanced disease has prompted the need to explore alternative therapeutic strategies. The challenge for oncology researchers is to identify a therapy which is selective for tumors with limited toxicity to normal tissue. Engineered bacteria have the unique potential to overcome traditional therapies' limitations by specifically targeting tumors. It has been shown that bacteria are naturally capable of homing to tumors when systemically administered resulting in high levels of replication locally, either external to (non-invasive species) or within tumor cells (pathogens). Pre-clinical and clinical investigations involving bacterial vectors require relevant means of monitoring vector trafficking and levels over time, and development of bacterial-specific real-time imaging modalities are key for successful development of clinical bacterial gene delivery. This review discusses the currently available imaging technologies and the progress to date exploiting these for monitoring of bacterial gene delivery in vivo.Cancer Gene Therapy ( INTRODUCTIONAlthough the potential anti-cancer effects of acquired bacterial infection have been evident for over 120 years and the presence of bacteria in excised tumors has been noted for over 60 years, 1 it is only in more recent times that the tumor-specific growth of bacteria has been considered for therapeutic purposes. While the precise mechanism(s) behind preferential bacterial tumor colonization remain poorly understood, this phenomenon must relate to unique tumor attributes that separate them from healthy tissues. Factors such as the irregular blood supply; local immune suppression; inflammation; and unique nutrient supply (e.g., purines) in tumors have been proposed to play a role. 2 Bacterial entry into the tumor environment is proposed to be facilitated by the leaky vasculature. Cancer cells are characterized by an aberrantly accelerated metabolism and proliferation leading to an imbalance of oxygen supply and consumption which is a major causative factor of tumor hypoxia. 3 The hypoxic nature of solid tumors enhances the growth of anaerobic and facultatively anaerobic bacteria. In addition, these areas with low oxygen and high interstitial pressure are considered to be an immunological sanctuary, where bacterial clearance mechanisms are greatly inhibited. 4 Necrotic regions are also rich in nutrients favoured by bacteria due to tumor cell turnover. However, tumor selective bacterial colonization now appears to be both bacterial species and tumor origin independent, since aerobic bacteria are also capable of colonising tumors, and even small tumors lacking an anaerobic center are colonised. See Figure 1 for proposed mechanisms.Invasive bacteria can internalize and replicate within tumor cells, while non-invasive bacteria grow externally to tumor cells, within the tumor micro-environment. 5 The tumor selective growth of bacteria has made them an attractive vehicle for the delivery of ...

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Section: Bacterial-mediated Tumor Therapymentioning

confidence: 99%

Bacterial vectors for imaging and cancer gene therapy: a review

et al. 2012

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“…Indeed, unlike previous bacterial therapies 11 , minimizing systemic circulation of drug-loaded MC-1 cells was achieved by initially guiding them (see Methods: magnetotaxis directional control) towards such OATZ where oxygen gradients could be detected by the bacteria. Magnetotaxis was first prioritized over aerota x is since, unlike hypoxic zones, the location of a tumour mass can generally be precisely determined.…”

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confidence: 99%

Magneto-aerotactic bacteria deliver drug-containing nanoliposomes to tumour hypoxic regions

et al. 2016

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Oxygen depleted hypoxic regions in the tumour are generally resistant to therapies1. Although nanocarriers have been used to deliver drugs, the targeting ratios have been very low. Here, we show that the magneto-aerotactic migration behaviour2 of magnetotactic bacteria3, Magnetococcus marinus strain MC-14, can be used to transport drug-loaded nanoliposomes into hypoxic regions of the tumour. In their natural environment, MC-1 cells, each containing a chain of magnetic iron-oxide nanocrystals5, tend to swim along local magnetic field lines and towards low oxygen concentrations6 based on a two-state aerotactic sensing system2. We show that when MC-1 cells bearing covalently bound drug-containing nanoliposomes were injected near the tumour in SCID Beige mice and magnetically guided, up to 55% of MC-1 cells penetrated into hypoxic regions of HCT116 colorectal xenografts. Approximately 70 drug-loaded nanoliposomes were attached to each MC-1 cell. Our results suggest that harnessing swarms of microorganisms exhibiting magneto-aerotactic behaviour can significantly improve the therapeutic index of various nanocarriers in tumour hypoxic regions.

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“…Also other non-pathogenic bacteria are currently under investigation for the delivery of genes selectively into tumor cells such as Lactococcus lactis and Escherichia coli [47]. Our results suggest that such an approach could be effective at young and old age.…”

Section: Discussionmentioning

confidence: 85%

Cancer Vaccination at Older Age

Gravekamp

2013

Cancer and Aging

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Cancer vaccination is less effective at old than at young age, due to T cell unresponsiveness. This is caused by various age-related changes of the immune system, such as lack of naïve T cells, defects in activation pathways of T cells and antigen-presenting cells, and age-related changes in the tumor microenvironment. Natural killer, natural killer T cells, and γδT cells of the innate immune system also change with age but these responses may be more susceptible for improvement than adaptive immune responses at older age. This chapter compares various studies involving adaptive and innate immune responses in elderly and cancer patients, as well as cancer vaccination at young and old age. Finally, potential new directions in cancer vaccination at older age are discussed. With the current rise of the elderly population, cancer is becoming an increasingly frequent disease and cause of death. From 2010 to 2030, the total projected cancer incidence in the United States for older adults will increase by approximately 67% [1]. Indeed, metastatic cancer has surpassed heart disease as the primary cause of death in people younger than age 85 [2]. Therefore, in spite of some improvements in prevention and treatment, metastatic cancer is now the most frequent cause of death in the elderly, with co-morbid conditions complicating further treatment. When metastatic, cancer often needs aggressive, second-line treatment, for which there are few options. This is particularly challenging for frail, elderly cancer patients in which co-morbidity plays an important role. Immunotherapy may be our best and most benign option for preventing or curing metastatic cancer in such patients. Unfortunately, cancer immunotherapy is less effective at old than at young age, due to T cell unresponsiveness, especially in the tumor microenvironment (TME) [3,4]. Various age-related changes of the immune system, such as lack of naïve T cells, defects in activation pathways of T cells and antigen-presenting cells (APC), and immune suppression in the TME contribute to T cell unresponsiveness at older age [4].

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Bacteria in cancer therapy: a novel experimental strategy

Cited by 280 publications

References 47 publications

Bacterial vectors for imaging and cancer gene therapy: a review

Bacterial vectors for imaging and cancer gene therapy: a review

Magneto-aerotactic bacteria deliver drug-containing nanoliposomes to tumour hypoxic regions

Cancer Vaccination at Older Age

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