<i>Salmonella typhimurium </i>Mediated Delivery of Apoptin in Human Laryngeal Cancer

Guan, Guofang; Ming, Zhao; Liu, Li Ming; Jin, Can; Sun, Kai; Zhang, Dejun; Yu, Duo‐Jiao; Cao, Hongwei; Lu, Yan; Wen, Lianji

doi:10.7150/ijms.6960

Cited by 30 publications

(18 citation statements)

References 38 publications

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“…Tumor specificity for secondary tumors and metastases has been extensively demonstrated and described for bacteria, in particular Salmonella [ 31 , 70 – 73 ]. It provides a solid argument for BMTT especially when combined with genetic cargo delivery [ 23 , 74 – 79 ]. This ability has been tied to a systemic route of inoculation.…”

Section: Discussionmentioning

confidence: 99%

Local application of bacteria improves safety ofSalmonella-mediated tumor therapy and retains advantages of systemic infection

et al. 2017

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Cancer is a devastating disease and a large socio-economic burden. Novel therapeutic solutions are on the rise, although a cure remains elusive. Application of microorganisms represents an ancient therapeutic strategy, lately revoked and refined via simultaneous attenuation and amelioration of pathogenic properties. Salmonella Typhimurium has prevailed in preclinical development. Yet, using virulent strains for systemic treatment might cause severe side effects. In the present study, we highlight a modified strain based on Salmonella Typhimurium UK-1 expressing hexa-acylated Lipid A. We corroborate improved anti-tumor properties of this strain and investigate to which extent an intra-tumoral (i.t.) route of infection could help improve safety and retain advantages of systemic intravenous (i.v.) application. Our results show that i.t. infection exhibits therapeutic efficacy against CT26 and F1.A11 tumors similar to a systemic route of inoculation. Moreover, i.t. application allows extensive dose titration without compromising tumor colonization. Adverse colonization of healthy organs was generally reduced via i.t. infection and accompanied by less body weight loss of the murine host. Despite local application, adjuvanticity remained, and a CT26-specific CD8 + T cell response was effectively stimulated. Most interestingly, also secondary tumors could be targeted with this strategy, thereby extending the unique tumor targeting ability of Salmonella. The i.t. route of inoculation may reap the benefits of systemic infection and aid in safety assurance while directing potency of an oncolytic vector to where it is most needed, namely the primary tumor.

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Section: Discussionmentioning

confidence: 99%

Local application of bacteria improves safety ofSalmonella-mediated tumor therapy and retains advantages of systemic infection

et al. 2017

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“…Lastly, more recent investigations have looked into the application of the chicken anemia virus derived protein “apoptin” as a passenger protein for vector-mediated anti-cancer treatment [ 150 ]. Guan et al , 2013 [ 110 ] successfully prolonged host survival in a syngeneic nude murine tumor model with marked tumor growth retardation and reduced microvessel density after systemic administration of apoptin-expressing S. Typhimurium.…”

Section: Live-attenuated Bacterial Vectors For Cancer Treatmentmentioning

confidence: 99%

Live-Attenuated Bacterial Vectors: Tools for Vaccine and Therapeutic Agent Delivery

2015

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Genetically attenuated microorganisms, including pathogenic and commensal bacteria, can be engineered to carry and deliver heterologous antigens to elicit host immunity against both the vector as well as the pathogen from which the donor gene is derived. These live attenuated bacterial vectors have been given much attention due to their capacity to induce a broad range of immune responses including localized mucosal, as well as systemic humoral and/or cell-mediated immunity. In addition, the unique tumor-homing characteristics of these bacterial vectors has also been exploited for alternative anti-tumor vaccines and therapies. In such approach, tumor-associated antigen, immunostimulatory molecules, anti-tumor drugs, or nucleotides (DNA or RNA) are delivered. Different potential vectors are appropriate for specific applications, depending on their pathogenic routes. In this review, we survey and summarize the main features of the different types of live bacterial vectors and discussed the clinical applications in the field of vaccinology. In addition, different approaches for using live attenuated bacterial vectors for anti-cancer therapy is discussed, and some promising pre-clinical and clinical studies in this field are outlined.

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“…Attenuated bacteria were have been used as a delivery vehicle to express cargo molecules, such as cytotoxic agents, 21 22 30 31 43 44 45 cytokines, 46 47 48 49 50 51 RNA interference, 52 53 54 55 56 57 and prodrug enzymes, 17 58 59 60 61 62 63 in tumors to enhance BCT ( Fig. 1 ).…”

Section: Key Features Of S Typhimurium That Make mentioning

confidence: 99%

Targeted Cancer Therapy Using EngineeredSalmonella typhimurium

Zheng

Min

2016

Chonnam Med J

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Obligate or facultative anaerobic bacteria such as Bifidobacterium, Clostridium, Salmonella, or Escherichia coli specifically colonize and proliferate inside tumor tissues and inhibit tumor growth. Among them, attenuated Salmonella typhimurium (S. typhimurium) has been widely studied in animal cancer models and Phase I clinical trials in human patients. S. typhimurium genes are easily manipulated; thus diverse attenuated strains of S. typhimurium have been designed and engineered as tumor-targeting therapeutics or drug delivery vehicles that show both an excellent safety profile and therapeutic efficacy in mouse models. An attenuated strain of S. typhimurium, VNP20009, successfully targeted human metastatic melanoma and squamous cell carcinoma in Phase I clinical trials; however, the efficacy requires further refinement. Along with the characteristics of self-targeting, proliferation, and deep tissue penetration, the ease of genetic manipulation allows for the production of more attenuated strains with greater safety profiles and vector systems that deliver designable cargo molecules for cancer diagnosis and/or therapy. Here, we discuss recent progress in the field of Salmonellae-mediated cancer therapy.

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Salmonella typhimurium Mediated Delivery of Apoptin in Human Laryngeal Cancer

Cited by 30 publications

References 38 publications

Local application of bacteria improves safety ofSalmonella-mediated tumor therapy and retains advantages of systemic infection

Local application of bacteria improves safety ofSalmonella-mediated tumor therapy and retains advantages of systemic infection

Live-Attenuated Bacterial Vectors: Tools for Vaccine and Therapeutic Agent Delivery

Targeted Cancer Therapy Using EngineeredSalmonella typhimurium

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