Adenoassociated Virus For Cancer Gene Therapy

Similar to the APV, wild-type AAV has also been identified to possess antioncogenic properties (62,63). Although rAAV vectors are relatively less studied in cancer gene therapy, those reported so far indicate their future potential. In addition, whereas most of the cancer gene therapy strategies target tumor cells directly for increasing therapeutic benefit, targeting normal cells that regulate key events conducive for tumor growth is becoming a promising alternative for cancer therapy. For...

Recombinant Apv For Cancer Gene Therapy

Although more than 30 different APV have been identified so far, most of the work has focused on vectors that can infect human cells namely LuIII, minute virus of mice (MVM), and parvovirus H1, which are members of rodent group of parvoviruses. Following the development of recombinant vectors based on AAV packaging by transcomplementing the vector proteins, similar strategies have been successfully tested with the APV including MVM, LuIII, and H1. MVM, one of the first parvoviruses to be...

Clinical Trials

As previousely discussed, adenovectors can effectively transduce in both dividing and nondividing cells in vivo and because long-term transgene expression is not a common prerequisite for cancer therapy, adenovectors are the most commonly used vector in cancer gene therapy (Journal of Gene Medicine Website, www.wiley.co.uk genmed clinical). The genes used in adenovector-mediated cancer therapy include tumor-suppressor genes (e.g., p53, Rb, and p16), prodrug activator or suicide genes (TKand...

Mien Chie Hung PhD and Duen Hwa Yan PhD

This chapter describes preclinical development of therapeutic genes in breast cancer treatment. Beginning from targeting HER-2 neu-overexpressing breast cancer cells by adenovirus E1A, we found E1A expression had profound effects on tumor cells including growth suppression, apoptosis, and sensitization to chemo-drugs and radiation. The mechanisms of the antitumor activities as well as the preliminary results obtained from multiple E1A clinical trials are discussed. Also identified are the...

Hypoxia

The hypoxic environment in solid tumors results from oxygen consumption by rapid proliferation of tumor cells. Hypoxia has been shown to facilitate the survival of tumor cells and to be a cause of malignant transformation thus playing a critical role in tumor biology (65). It inhibits TNF-related apoptosis-inducing ligand (TRAIL) -induced apoptosis by blocking Bax translocation to the mitochondria (65). Intratumoral hypoxia has been shown to be a prognostic parameter in variety of human cancers...

Glen N Barber PhD Contents

Genetically Engineering RNA Viruses and VSV The ability of RNA viruses to efficiently reproduce in transformed cells was first recognized nearly 100 yr ago. However, it wasn't until the late 1990s that a resurrection of the interest in the ability of certain viruses to preferentially replicate in malignant cells and less so in normal cells occurred, the curiosity being to evaluate whether these agents could be useful in cancer therapy regimes. It was following these reports, demonstrating that...

Selvarangan Ponnazhagan PhD

Molecular Organization of Parvoviruses Production of Recombinant Parvoviruses Recombinant APV for Cancer Gene Therapy Adeno-Associated Virus for Cancer Gene Therapy Adeno-Associated Virus-Mediated Long-Term Expression for Cancer Therapy Adeno-Associated Virus for Immunotherapy Recombinant AAV-Mediated Cancer Gene Therapy as Adjuvant Therapy Conclusion Acknowledgments Parvoviruses are among the smallest of eukaryotic viruses. The association of parvovirus with cancer has been reported much...

Cytokine Modified Macrophages

Tumor associated macrophages are inversely correlated with tumor progression in human prostate cancer 104 and they may provide important antigen presenting functions in an antitumor immune response. Studies have revealed that in radical prostatectomy specimens the macrophage marker scavenger receptor A MSR-A was expressed in a subset of macrophages and DCs that infiltrated prostatic tissues. The majority of MSR-A positive cells were macrophages as evidenced by coexpression of CD68 and a...

Vaccinia As An Oncolytic Virus For Cancer Therapy

The concept of a tumor selective oncolytic virus that can be safely administered is very appealing and is the focus of current research by multiple laboratories. The advantages of the vaccinia virus as an oncolytic virus have been described earlier in the chapter. The most important advantage is the efficiency of viral replication, cell to cell spread and ability to destroy tissue. Development of an oncolytic virus has focused on genetic alterations of the WR strain of virus to achieve a tumor...

Kenneth Lundstrom PhD Contents

Alphavirus for the Transfection of Tumor Cell Lines Intratumoral Gene Delivery by Alphavirus Tumor Targeting of Alphavirus Vectors Production of Retrovirus-Like Particles by Alphavirus Alphavirus vectors can infect a broad range of mammalian cells both in cell cultures and in vivo. The presence of the RNA replicon generates extreme RNA levels in infected cells, which is the basis for the very high levels of heterologous gene expression. Application of replication-deficient vectors leads to...

Preface

The possibility of treating cancer, a disease defined by genetic defects, by introducing genes targeting these very alterations has led to an immense interest in gene therapy for cancer. Although incremental successes have been realized, enthusiasm for gene therapy has declined due to an increasing number of obstacles. These obstacles include vector systems that do not reach systemic metastases, therapeutic genes with redundant mechanisms allowing for cellular resistance, and toxicities in...

Adenovector Mediated Cancer Gene Therapy

Roth, md Vector-Related Toxicity and Safety Issues Early-region E1 -deleted, replication-defective adenovectors have been widely used in preclinical and clinical studies of cancer gene therapy. Recently, the use of conditional replicating or oncolytic adenovectors in cancer gene therapy or virotherapy has received much attention. Clinical trials with E1-deleted adenovectors and oncolytic adenovirus have shown that adenovector-mediated cancer gene therapy is...