Articles That Are Related to Article:

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


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

RNA Interference and Personalized Cancer Therapy

Abstract: Despite billions of dollars allocated to cancer research, cancer remains the number 2 cause of death in the United States with less than 50% of advanced cancer patients living one year following standard treatment. Cancer is a complex disease both intrinsically and in relation to its host environment. From a molecular standpoint no two cancers are the same despite histotypic similarity. As evidenced by the recent advances in molecular biology, treatment for advanced cancer is headed towards specific targeting of vulnerable signaling nodes within the reconfigured pathways created by "omic" rewiring. With advancements in proteo-genomics and the capacity of bioinformatics, complex tumor biology can now be more effectively and rapidly analyzed to discover the vulnerable high information transfer nodes within individual tumors. RNA interference (RNAi) technology, with its capability to knock down the expression of targeted genes (the vulnerable nodes), is moving into the clinic to target these nodes, which are integral to tumor maintenance, with a low risk of side-effects and to block intrinsic immunosuppressors thereby priming the tumor for immune attack. An RNAi based sequential approach, a so called "one-two punch," is being advocated comprising tumor volume reduction (ideally to minimal residual disease status) effected by integrated multi-target knockdown followed by immune activation. Examples and recent developments are provided to illustrate this highly powerful approach heralding the future of personalized cancer therapy. ... Read more

Innovative Approaches for Enhancing Cancer Gene Therapy

Abstract: Gene therapy provides a novel platform for therapeutic intervention of several genetic and non-genetic disorders. With the recent developments in the field, a wide variety of viral and non-viral vectors have emerged that can deliver genetic payloads to target cells. However, non-targeted delivery of transgenes often results in undesirable effects, low tumor transduction, and reduced therapeutic index. In this review, we focus on some of the novel approaches that can be used to meet the present challenges in the field and translate the potential of cancer gene therapy from 'bench to bedside' in the near future. ... Read more

Editor's Note -- February 2005

For many of the difficult-to-treat diseases, gene-based therapies and gene-based drug deliveries offer hope and excitement. In this issue of Discovery Medicine, articles describe the use of gene therapy to manipulate stem cells for treating heart diseases (Dr. Rosen et al. on page 18), to produce vaccines for the immunotherapy of cancer (Dr. Acres et al. on page 25 and Dr. Stevenson on page 37), and to fight HIV-1 infection (Dr. Egan on page 58).

However since their first use about two decades ago, gene therapies have remained experimental. Genes with therapeutic potential have been injected into test animals and patients ... 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

Targeted, Gene-directed Enzyme Prodrug Therapies to Tackle Diversity and Aggression of Late Stage Prostate Cancer

Abstract: Late stage hormone refractory prostate cancer (HRPC) is presently incurable. Novel alternatives such as cytoreductive Gene Directed Enzyme Prodrug Therapy (GDEPT) offer great hope: The potential for in situ amplification of cytotoxicity due to GDEPT-associated "bystander effects" has special appeal for patients with prostate cancer, the prostate being dispensable. In this overview, recent developments in various GDEPT systems for treating prostate cancer are described. Research related to the enhancement of in situ GDEPT delivery and prostate cancer-targeting of viral vectors, is reviewed. The scope and progress of synergies between GDEPT and other treatment modalities, traditional and alternate, are discussed. ... Read more

Modified Adeno-associated Virus (AAV) Vectors: A New Generation of Targeted Gene Therapy Delivery Systems

Gene therapy in its simplest form is the deliberate transfer of therapeutic genes into a host cell. As a human gene therapy vector, Adeno-Associated Virus (AAV) is a promising delivery system. It is able to maintain stable gene expression in host cells, is efficient at gene delivery in vivo, and is non-pathogenic. However, one obstacle facing the advancement of AAV vectors is the natural tropism of the virus. The primary attachment receptor for AAV type-2 (AAV2) is heparan sulfate proteoglycan (HSPG). This receptor is widely expressed on many cell types, which creates a problem when delivering genes that promote cell ... Read more

Gene Therapy for Cancer: Dairy Bacteria as Delivery Vectors

Abstract: The prime obstacle to achieving an effective treatment for cancer is that of eradicating tumors without harming healthy organs and cells of the patient. The concept of utilizing biological agents for delivery of therapeutic genes to patients to kill cancer cells has been under investigation for two decades, which exploits the natural ability of disease causing microbes to invade human cells. Safety-modified versions of pathogenic viruses or bacteria can deposit genes and induce production of anti-cancer agents upon administration to tumors and promising clinical trial successes have been achieved with various types of gene delivery vehicles. Bacteria present an attractive class of gene vectors, possessing a natural ability to grow specifically within tumors following intravenous (IV) injection. Several species such as Clostridium and Salmonella have been examined in clinical trials. However, as foreign, disease-causing bugs, their inherent toxicity has outweighed therapeutic responses in patients, despite efforts to reduce toxicity through genetic modification. A promising alternative exploits non-pathogenic bacterial species that have an existing natural relationship with humans. Our recent study (Cronin et al., 2010) has demonstrated that IV injection or ingestion of a species of probiotic bacterium, Bifidobacterium breve, in high numbers, results in trafficking of the bacteria throughout the body and accumulation specifically within cancerous tissue. ... Read more

Recent Breakthroughs in Gene Therapy for Inherited Retinal Degeneration

Abstract: Gene therapy for inherited retinal degeneration has made major advances toward the ultimate goal of reversing blindness in human patients. With significant advances in recombinant viral vector design, safety and efficacy profiles have greatly improved. Although these recent advances have been applied to many different retinal diseases, one retinal degenerative disease, Leber congenital amaurosis, appears to have the greatest potential for reversing blindness. In pre-clinical animal studies, gene therapy for Leber congenital amaurosis has demonstrated visual recovery. Recently, in landmark clinical trials, preliminary results have indicated safety and efficacy for the use of gene therapy in Leber congenital amaurosis, thus laying the foundation for continued use of gene therapy in other forms of inherited blinding disease. ... Read more

MicroManipulating Viral-based Therapeutics

Abstract: Despite the social stigma and manufacturing hurdles that come with using viruses as therapeutic tools, the molecular specificity offered by these bugs makes them too attractive to ignore. Still largely based on vaccines, viral vectors offer exciting tools to treat cancer or deliver specific genetic payloads to a desired tissue. Unfortunately, early clinical trials utilizing such vectors have been plagued with poor performance or even clinical toxicity most commonly associated with spurious genetic regulation and/or replication of the vector. Past efforts to control for unwanted toxicity have focused on modification of the receptor or use of tissue-specific genetic elements that added specificity to the transcriptional induction of the gene(s) of interest. While this has had some success, engineering receptors to control viral tropism often fails or results in a loss of replicative fitness. In addition, the use of tissue-specific promoter elements not only restricts the vector that can be used, bona fide small promoter elements are often not available for the desired target. With the caveats of viral vector-based therapeutics largely centered on a lack of in vivo control, the recent success of exploiting microRNA expression to limit viral tropism may breathe new life into the field. ... Read more

Close
Close
E-mail It
Close