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1.
J Immunother Cancer ; 6(1): 78, 2018 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-30081947

RESUMO

In this White Paper, we discuss the current state of microbial cancer therapy. This paper resulted from a meeting ('Microbial Based Cancer Therapy') at the US National Cancer Institute in the summer of 2017. Here, we define 'Microbial Therapy' to include both oncolytic viral therapy and bacterial anticancer therapy. Both of these fields exploit tumor-specific infectious microbes to treat cancer, have similar mechanisms of action, and are facing similar challenges to commercialization. We designed this paper to nucleate this growing field of microbial therapeutics and increase interactions between researchers in it and related fields. The authors of this paper include many primary researchers in this field. In this paper, we discuss the potential, status and opportunities for microbial therapy as well as strategies attempted to date and important questions that need to be addressed. The main areas that we think will have the greatest impact are immune stimulation, control of efficacy, control of delivery, and safety. There is much excitement about the potential of this field to treat currently intractable cancer. Much of the potential exists because these therapies utilize unique mechanisms of action, difficult to achieve with other biological or small molecule drugs. By better understanding and controlling these mechanisms, we will create new therapies that will become integral components of cancer care.


Assuntos
Bactérias , Terapia Biológica/métodos , Vetores Genéticos , Neoplasias/prevenção & controle , Neoplasias/terapia , Vírus , Animais , Bactérias/genética , Terapia Biológica/normas , Terapia Biológica/tendências , Vacinas Anticâncer/genética , Vacinas Anticâncer/imunologia , Estudos Clínicos como Assunto , Terapia Combinada , Avaliação Pré-Clínica de Medicamentos , Engenharia Genética , Vetores Genéticos/genética , Humanos , Neoplasias/etiologia , Terapia Viral Oncolítica , Resultado do Tratamento , Vírus/genética
2.
Magn Reson Med ; 70(6): 1690-8, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24123389

RESUMO

PURPOSE: To develop a noninvasive MRI method for determining the germination and infection of tumor-homing bacteria in bacteriolytic cancer therapy using endogenous CEST contrast. METHODS: The CEST parameters of the anaerobic gram-positive bacterium Clostridium novyi-NT (C. novyi-NT) were first characterized in vitro, then used to detect C. novyi-NT germination and infection in subcutaneous CT26 colorectal tumor-bearing mice (n = 6) after injection of 300 million bacterial spores. Lipopolysacharide (LPS) injected mice were used to exclude that the changes of CEST MRI were due to inflammation. RESULTS: CEST contrast was observed over a broad frequency range for bacterial suspensions in vitro, with the maximum contrast around 2.6 ppm from the water resonance. No signal could be detected for bacterial spores, demonstrating the specificity for germination. In vivo, a significant elevation of CEST contrast was identified in C. novyi-NT infected tumors as compared to those before bacterial germination and infection (P < 0.05; n = 6). No significant change was observed in tumors with LPS-induced sterile inflammation (P > 0.05; n = 4). CONCLUSION: Endogenous bacterial CEST contrast (bacCEST) can be used to monitor the germination and proliferation of the therapeutic bacterium C. novyi-NT without a need for exogenous cell labeling probes.


Assuntos
Infecções por Clostridium/patologia , Clostridium/isolamento & purificação , Clostridium/fisiologia , Neoplasias Colorretais/terapia , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Animais , Terapia Biológica/métodos , Linhagem Celular Tumoral , Infecções por Clostridium/microbiologia , Neoplasias Colorretais/microbiologia , Neoplasias Colorretais/patologia , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
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