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Gene Therapy for Cancer: Dairy Bacteria as Delivery Vectors


Vaccine Adjuvant Properties of Probiotic Bacteria

Abstract: Vaccine-preventable diseases are still responsible for the deaths of more than 1 million children under the age of 5 years annually, mostly in developing countries. A substantial number of these deaths are due to pneumococcal bacteria and infections with rotavirus. Important issues faced by the WHO, governments, vaccine manufacturers, and international organizations such as UNICEF and the Global Alliance for Vaccines and Immunization (GAVI) are the cost-effective introduction of these life-saving vaccines in resource-poor countries where there is a considerable disease burden, and achieving high rates of completion of vaccination schedules remains elusive. Problems with vaccine coverage and vaccine delivery in these regions are significant, as in some cases large proportions of the target population do not receive adequate vaccination. Consequently, there is a need to develop more effective vaccination strategies that can provide adequate protection with reduced schedules. To date, emphasis has been placed on identifying novel vaccine antigens and adjuvants that induce stronger protective immune responses, as well as developing mucosally-administered vaccines. These approaches would have enormous benefits in allowing safe administration of vaccines in remote areas and may overcome the necessity for multiple doses. In this regard, the use of probiotic bacteria as novel mucosal adjuvants to enhance existing vaccine specific-immune responses offers an exciting new approach. In this review, we discuss the evidence for the role of probiotics in enhancing vaccine responses and provide justification for further investigation into their clinical effects and mechanisms of action. ... Read more

Probiotics -- A Viable Therapeutic Alternative for Enteric Infections Especially in the Developing World

Abstract: This review focuses on the most recent advances in the application of probiotics as potential therapeutics for the developing world, from the treatment of chronic and acute enteric infections and their associated diarrheal complexes to the development of designer probiotics for controlling HIV and as novel mucosal vaccine delivery vehicles. ... Read more

Gene Therapy and Virotherapy: Novel Therapeutic Approaches for Brain Tumors

Abstract: Glioblastoma multiforme (GBM) is a deadly primary brain tumor in adults, with a median survival of ~12-18 months post-diagnosis. Despite recent advances in conventional therapeutic approaches, only modest improvements in median survival have been achieved; GBM usually recurs within 12 months post-resection, with poor prognosis. Thus, novel therapeutic strategies to target and kill GBM cells are desperately needed. Our group and others are pursuing virotherapy and gene therapy strategies for the treatment of GBM. In this review, we will discuss various virotherapy and gene therapy approaches for GBM currently under pre-clinical and clinical evaluation including direct or conditional cytotoxic, and/or immunostimulatory approaches. We also discuss cutting-edge technologies for drug/gene delivery and targeting brain tumors, including the use of stem cells as delivery platforms, the use of targeted immunotoxins, and the therapeutic potential of using GBM microvesicles to deliver therapeutic siRNAs or virotherapies. Finally, various animal models available to test novel GBM therapies are discussed. ... Read more

Gene-directed Enzyme Prodrug Therapy for Cancer: A Glimpse into the Future?

Abstract: Gene-directed enzyme prodrug therapy offers a new approach to treating some cancers. Clinical trials have been completed for brain and prostate cancers and the first product for post-surgical treatment of some brain tumors is awaiting marketing approval. Recent innovations provide a glimpse into the possible future evolution of a new gene medicine. ... Read more

State-Of-The-Art Human Gene Therapy: Part I. Gene Delivery Technologies

Abstract: Safe and effective gene delivery is a prerequisite for successful gene therapy. In the early age of human gene therapy, setbacks due to problematic gene delivery vehicles plagued the exciting therapeutic outcome. However, gene delivery technologies rapidly evolved ever since. With the advancement of gene delivery techniques, gene therapy clinical trials surged during the past decade. As the first gene therapy product (Glybera) has obtained regulatory approval and reached clinic, human gene therapy finally realized the promise that genes can be medicines. The diverse gene delivery techniques available today have laid the foundation for gene therapy applications in treating a wide range of human diseases. Some of the most urgent unmet medical needs, such as cancer and pandemic infectious diseases, have been tackled by gene therapy strategies with promising results. Furthermore, combining gene transfer with other breakthroughs in biomedical research and novel biotechnologies opened new avenues for gene therapy. Such innovative therapeutic strategies are unthinkable until now, and are expected to be revolutionary. In part I of this review, we introduced recent development of non-viral and viral gene delivery technology platforms. As cell-based gene therapy blossomed, we also summarized the diverse types of cells and vectors employed in ex vivo gene transfer. Finally, challenges in current gene delivery technologies for human use were discussed. ... Read more

The Impact of Antibiotics on the Gut Microbiota as Revealed by High Throughput DNA Sequencing

Abstract: Treatment with broad spectrum antibiotics can have a detrimental impact on the commensal bacteria present in the gut. The extensive nature of the collateral damage caused by such compounds has been revealed more starkly than ever before through the application of high throughput DNA sequencing-based technologies to investigate resulting microbial populations. Here we review the findings of such studies and discuss the strategies available to minimize such negative impacts. ... Read more

Editor's Note -- August 2005

“Between 500 and 1,000 microbial species colonize the mammalian colon to a density of approximately 1012 bacteria per gram of content, comprising in total 100 times more cells than those that make up the host itself,” said Drs. Lanning and Knight in an article published in this issue of the journal. Given the immensity of the bacteria living inside our bodies, it is almost a miracle that they do not cause more trouble than they occasionally do (e.g., diarrhea, enterocolitis, imbalance of intestinal flora, etc.).

On the contrary, the commensal bacterial flora in the gut performs important, unconventional tasks ... Read more

Gene-based Cancer Immunotherapy and Vaccines

Abstract: Cancer treatment has been marred by the fact that most drugs target cancer cells as well as normal cells. Gene therapy is one of a handful of methods that will make cancer cells "stand out," allowing drugs or the host's immune system to selectively target cancer cells. ... Read more

Gene Therapy: A Possible Aid to Cancer Radiotherapy

Abstract: Radiotherapy and gene therapy seem far apart. Nevertheless, they can form a formidable partnership in killing cancer cells. Gene delivery technology can make cancer cells more vulnerable to radiation therapy and make surrounding normal cells more resistant to it. ... Read more

Stem Cell-mediated Gene Therapies for Malignant Gliomas: A Promising Targeted Therapeutic Approach?

Abstract: Glioblastomas are aggressive intrinsic brain tumors. The median overall survival does not exceed 15 months despite surgical resection, radiotherapy, and chemotherapy even in selected clinical trial populations. One reason for this poor outcome is the characteristic infiltrative growth pattern of glioblastomas with tumor cells deeply infiltrating into the normal brain parenchyma and thereby escaping surgical debulking and involved-field radiation therapy. Novel therapeutic strategies are urgently needed including those that target disseminated tumor cells, too. In this regard, the application of adult stem cells as cellular vehicles for the delivery of therapeutic molecules has emerged during the last decade as an experimental approach. Adult stem cells with a tropism for gliomas include neural stem and progenitor cells, mesenchymal stem cells, hematopoietic progenitor cells, and endothelial progenitor cells. Importantly, these candidate cellular carriers also localize to sites of hypoxia and invasive tumor borders which are usually not targeted by currently available therapeutic approaches. Stem cell-based therapeutic approaches could therefore help to overcome some of the current limitations of radio- and chemotherapy and may circumvent toxicity to normal resident cells of the central nervous system. The development of neural stem- and progenitor-based therapies is advanced with a currently ongoing phase I clinical study. We review rationale, achievements, and future challenges in this field. ... Read more

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