Cancer immunotherapy using recombinant Listeria monocytogenes Transition from bench to clinic
ABSTRACT Cancer immunotherapy has developed into a field of intense study as aspects of the immune system involved in the eradication of cancer have become delineated. Listeria monocytogenes is a gram-positive, facultative intracellular bacterium which infects antigen presenting cells (APC), and is being used as a cancer vaccine to deliver tumor antigens directly to the APC. This results in the generation of a strong immune response towards the tumor associated antigen and direct targeting of the tumor by the immune system. Advances in this field have led to the development of a series of L. monocytogenes-based cancer vaccines, which are currently in clinical trials. A phase I study has shown these vaccines can be safely administered and well-tolerated in terminal stage cancer patients and an efficacy signal was observed in patients who did not respond to other therapies. Additional data on the efficacy of these vaccines is expected in the near-term.
SourceAvailable from: Dominik Czaplicki[Show abstract] [Hide abstract]
ABSTRACT: Bacterial cancer therapy is a concept more than 100 years old - yet, all things considered, it is still in early development. While the use of many passive therapeutics is hindered by the complexity of tumor biology, bacteria offer unique features that can overcome these limitations. Microbial metabolism, motility and sensitivity can lead to site-specific treatment, highly focused on the tumor and safe to other tissues. Activation of tumor-specific immunity is another important mechanism of such therapies. Several bacterial strains have been evaluated as cancer therapeutics so far, Salmonella Typhimurium being one of the most promising. S. Typhimurium and its derivatives have been used both as direct tumoricidal agents and as cancer vaccine vectors. VNP20009, an attenuated mutant of S. Typhimurium, shows significant native toxicity against murine tumors and was studied in a first-in-man phase I clinical trial for toxicity and anticancer activity. While proved to be safe in cancer patients, insufficient tumor colonization of VNP20009 was identified as a major limitation for further clinical development. Antibody-fragment-based targeting of cancer cells is one of the few approaches proposed to overcome this drawback.Acta biochimica Polonica 07/2013; · 1.39 Impact Factor
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ABSTRACT: Current conventional treatments for cancer lack tumour selectivity resulting in the destruction of healthy tissue and severe adverse effects to the patient in addition to limiting the administration dose and efficacy. Hence, it is imperative that we seek alternative approaches to treat cancer that localise therapeutic agents to the site of the tumour and spare normal tissue. The use of bacteria in cancer therapy represents one such approach. Bacteria were first used as anti-cancer agents over a century ago. Today, this field has re-emerged from the past and is progressing at a rapid rate. Bacteria are used as anticancer agents either alone or in combination with conventional treatments and have been armed with an arsenal of therapeutic genes, which enhance their efficacy. Bacterial directed enzyme prodrug therapy (BDEPT) is one of the most promising approaches, which harnesses the tumour-specific location of bacteria to locally activate systemically administered 'prodrugs' within the tumour in order to induce selective tumour destruction. BDEPT is a relatively new concept. It was originally conceived more than 10 years ago but it is only until recently that we witness a surge in activity in this field. In this review, we provide a full account of developments in the field of BDEPT since its inception. We share technical knowhow and discuss optimization strategies for vector and enzyme combinations, provide a clear view of the research landscape and suggest possible directions for the field.Journal of Controlled Release 08/2013; DOI:10.1016/j.jconrel.2013.05.005 · 7.63 Impact Factor
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ABSTRACT: In the emerging field of active and specific cancer immunotherapy, strategies using live-attenuated bacterial vectors have matured in terms of academic and industrial development. Different bacterial species can be genetically engineered to deliver antigen to APCs with strong adjuvant effects due to their microbial origin. Proteic or DNA-encoding antigen delivery routes and natural bacterial tropisms might differ among species, permitting different applications. After many academic efforts to resolve safety and efficacy issues, some firms have recently engaged clinical trials with live Listeria or Salmonella spp. We describe here the main technological advances that allowed bacteria to become one of the most promising vectors in cancer immunotherapy.Expert Review of Vaccines 10/2013; 12(10):1139-1154. DOI:10.1586/14760584.2013.836914 · 4.22 Impact Factor