Immunotherapeutic potential of DISC-HSV and OX40L in cancer

Assudani, Deepak; Ahmad, Murrium; Geng, Lanlan; Rees, Robert C.; Ali, Selman A.

doi:10.1007/s00262-005-0004-y

Cited by 13 publications

(6 citation statements)

References 62 publications

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“…An initial study demonstrated the presence of immunogenic MHC class I-restricted peptides of MTA1. 169…”

Section: The Methodology For Identifying Of Mi-2/nurd Complex Composimentioning

confidence: 99%

The Expanding Mi-2/NuRD Complexes: A Schematic Glance

Zhang

2010

Proteomics�Insights

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This mini-review will schematically update the progress of the expanding Mi-2/Nucleosome Remodeling Deacetylase (NuRD) complexes in cancer and in normal development such as stemness, with a focus on mammals and the increasingly popular and powerful model organism Caenorhabditis elegans. The Mi-2/NuRD complexes control gene activity during the development of complex organisms. Every Mi-2/NuRD complex contains many different core polypeptides, which form distinct multifunctional complexes with specific context-dependent regulators. The Mi-2/NuRD complexes have unique ATP-dependent chromatin remodeling, histone deacetylase, demethylase activities and higher order chromatin organization. They can regulate the accessibility of transcription factors or repair proteins to DNA. In this review, we summarize our current knowleges in the composition, interaction and function of the subunits within the Mi-2/NuRD complex, the methodology used for the identification of Mi-2/NuRD complexes, as well as the clinical and therapeutic implications targeting the Mi-2/NuRD subunits.

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“…An initial study demonstrated the presence of immunogenic MHC class I-restricted peptides of MTA1. 169…”

Section: The Methodology For Identifying Of Mi-2/nurd Complex Composimentioning

confidence: 99%

The Expanding Mi-2/NuRD Complexes: A Schematic Glance

Zhang

2010

Proteomics�Insights

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“…In a review on a model for immunotherapy using a vector, disabled infectious single cycle-herpes simplex virus (DISC-HSV), Assudani et al [77] proposed that MTA1 is a promising antigen for tumor rejection, because it is greatly overexpressed in many different tumors and is only expressed at lower levels in normal tissues. Their initial studies demonstrated the presence of immunogenic MHC class I-restricted peptides of MTA1.…”

Section: Mta Proteins As New Molecular Targets: Clinical Implicationsmentioning

confidence: 99%

The role of the MTA family and their encoded proteins in human cancers: molecular functions and clinical implications

Toh

Nicolson

2008

Clin Exp Metastasis

193

191

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MTA (metastasis-associated gene) is a newly discovered family of cancer progression-related genes and their encoded products. MTA1, the first gene found in this family, has been repeatedly reported to be overexpressed along with its protein product MTA1 in a wide range of human cancers. In addition, the expression of MTA1/MTA1 correlates with the clinicopathological properties (malignant properties) of human cancers. MTA proteins are transcriptional co-repressors that function in histone deacetylation and are involved in the NuRD complex, which contains nucleosome remodeling and histone deacetylating molecules. MTA1 expression correlates with tumor formation in the mammary gland. In addition, MTA1 converts breast cancer cells to a more aggressive phenotype by repression of the estrogen receptor (ER) alpha trans-activation function through deacetylation of the chromatin in the ER-responsive element of ER-responsive genes. Furthermore, MTA1 plays an essential role in c-MYC-mediated cell transformation. Another member of this family, MTA3, is induced by estrogen and represses the expression of the transcriptional repressor Snail, a master regulator of "epithelial to mesenchymal transitions", resulting in the expression of the cell adhesion molecule E-cadherin and maintenance of a differentiated, normal epithelial phenotype in breast cells. In addition, tumor suppressor p53 protein is deacetylated and inactivated by both MTA1 and MTA2, leading to inhibition of growth arrest and apoptosis. Moreover, a hypoxia-inducible factor-1alpha (HIF-1alpha) is also deacetylated and stabilized by MTA1, resulting in angiogenesis. Thus, MTA proteins, especially MTA1, represent a possible set of master co-regulatory molecules involved in the carcinogenesis and progression of various malignant tumors. MTA proteins are proposed to be important new tools for clinical application in cancer diagnosis and treatment.

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“…At the preclinical level, it may be instructive to directly compare the immunogenicity of helper-containing and helper-free amplicon stocks in a range of experimental animal model systems, and to also compare responses to those elicited by replicationdefective HSV-1 vectors encoding matched inserts -such as the DISC vector system originally developed by Minson and others [Ali et al, 2002;Assudani et al, 2005;Farrell et al, 1994;McLean et al, 1994], or the recombinant HSV vaccine strains being studied by Knipe and coworkers [Da Costa et al, 2000;Da Costa et al, 1999;Da Costa et al, 2001;Murphy et al, 2000]. It will also be important to evaluate the immunogenicity of amplicon vectors following mucosal delivery, in light of the natural ability of HSV-1 to infect mucosal surfaces, and to test their ability to elicit immune responses in nonhuman primates -including animals that have pre-existing immunity to HSV-1.…”

Section: Future Needs and Clinical Trans-lationmentioning

confidence: 99%

Amplicons as Vaccine Vectors

Santos¹,

Duke²,

Dewhurst³

2006

CGT

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HSV-1 amplicon vectors efficiently transduce cultured antigen-presenting cells (APC), including both human and murine dendritic cells as well as primary human chronic lymphocytic leukemia (CLL) B cells. Helper-free amplicons have been shown to be especially well-suited for this purpose, since they do not impair the antigen-presenting functions of these target cells. In vivo, amplicon vectors have been used in preclinical studies aimed at the development of therapeutic cancer vaccines, as well as vaccines for Alzheimer's disease, and selected microbial pathogens. Studies in small animal model systems have shown that ex vivo transduction of irradiated tumor cells with amplicon vectors encoding immunomodulatory cytokines such as IL-2 or GM-CSF can elicit protective responses against a tumor challenge. In an experimental model for cancer immunotherapy, direct transduction of preformed tumors with vectors encoding CD40L resulted in slowed tumor growth or tumor eradication. Other studies have examined the ability of amplicons to elicit immune responses against encoded antigens, and have shown that strong cellular immune responses can be generated against amplicon encoded HIV-1 antigens in mice. Thus, amplicon vectors have shown significant promise as vaccine vectors in a range of settings. These promising initial findings highlight the need to perform additional studies, including experiments to evaluate the immunogenicity of amplicon vectors in additional animal models, possibly including nonhuman primates. Overall, amplicon vectors offer compelling advantages when compared to other vaccine-delivery platforms, which include the capacity to incorporate a very large transgene payload and the potential to efficiently transduce mucosal surfaces. It will be important to design future studies to directly test and exploit these features of the amplicon system. The next few years therefore promise to be an exciting and important period in the development of amplicons as vaccine vectors.

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Immunotherapeutic potential of DISC-HSV and OX40L in cancer

Cited by 13 publications

References 62 publications

The Expanding Mi-2/NuRD Complexes: A Schematic Glance

The Expanding Mi-2/NuRD Complexes: A Schematic Glance

The role of the MTA family and their encoded proteins in human cancers: molecular functions and clinical implications

Amplicons as Vaccine Vectors

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