Alloantigen Gene Therapy for Squamous Cell Carcinoma of the Head and Neck

Gleich, Lyon L.; Gluckman, Jack L.; Armstrong, Shanna; Biddinger, Paul; Miller, Mary Ann; Balakrishnan, Kamala; Wilson, Keith; Saavedra, Harold I.; Stambrook, Peter J.

doi:10.1001/archotol.124.10.1097

Cited by 39 publications

(13 citation statements)

References 28 publications

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“…17 Cationic liposomes have been used in the phase I setting in HNSCC to deliver a variety of genes including HLA-B7, IL-2 and ElA. [18][19][20] We used the cationic derivative of cholesterol, DC-Chol. These cationic liposomes were mixed with plasmid DNA encoding an EGFR antisense gene.…”

Section: Discussionmentioning

confidence: 99%

Tissue distribution of liposome-mediated epidermal growth factor receptor antisense gene therapy

et al. 2003

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Despite the widespread use of liposome-mediated gene transfer in cancer therapy protocols, little is known about the tissue distribution of intralesionally administered DNA. We have previously shown that antisense gene therapy targeting the epidermal growth factor receptor (EGFR) inhibited tumor growth in a human head and neck squamous cell carcinoma (HNSCC) xenograft model. Further investigation demonstrated lack of systemic toxicity with intramuscular or intratumoral administration of this liposomal-DNA complex. In the present study, we compared two approaches to determine the presence of exogenous DNA in the plasma and tissues of mice treated with intramuscular injection of EGFR antisense gene therapy. PCR analysis using genomic DNA plus plasmid DNA as template was 83-fold more sensitive than PCR using a mixture of total RNA and plasmid DNA as template. With the more sensitive method (able to detect fewer than 500 molecules of EGFR antisense DNA in 1 mg of genomic DNA), foreign DNA was detected in all organs up to 1 month following a single injection. In contrast, using RNA plus plasmid DNA as template, exogenous DNA was only detected at the injection site at 1 week, and was undetectable at 1 month. Optical imaging studies demonstrated plasmid DNA only at the injection site. Although less sensitive than PCCR, Southern blot hybridization showed no evidence of integration of foreign DNA into the host genome in vitro or in vivo. These results emphasize the importance of defining the assays used to detect foreign DNA and suggest that the ability to detect intralesionally administered liposomal gene therapy, in organs distant from the injection site, is directly correlated with the sensitivity of the method employed.

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Section: Discussionmentioning

confidence: 99%

Tissue distribution of liposome-mediated epidermal growth factor receptor antisense gene therapy

et al. 2003

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“…Further, rejection of leukemic cells has been reported after gene transfer of MHC (Hui et al, 1984). On the basis of these studies an MHC alloantigen gene therapy strategy was developed and tested in preclinical models and in patients with HNSCC (Gleich et al, 1998(Gleich et al, , 2001(Gleich et al, , 2003. Allovectin-7 (Vical, San Diego, CA) is plasmid DNA formulation that expresses the allo-MHC class I molecule HLA-B7 heavy chain and b 2 -microglobulin required for stabilization of HLA-B7.…”

Section: Immune-modulatory Gene Therapymentioning

confidence: 99%

“…Liposomes have been used clinically and are nontoxic when administered at low concentrations. Cationic liposomes have been used to deliver several genes including those encoding HLA-B7, interleukin (IL)-2, and E1A (Gleich et al, 1998;Wollenberg et al, 1999;Yoo et al, 2001). Unlike some viral vectors, liposomes do not facilitate the integration of plasmid DNA into genomic DNA, necessitating retreatment.…”

mentioning

confidence: 99%

The Current State of Head and Neck Cancer Gene Therapy

Thomas

Grandis²

2009

Human Gene Therapy

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The incidence of head and neck cancer continues to increase worldwide, with tobacco exposure and human papillomavirus type 16 infections being the major etiological factors. Current therapeutic options are ineffective in approximately half of the individuals afflicted with this malignancy. Developments in the identification of molecules that sustain head and neck squamous cell carcinoma (HNSCC) growth and survival have made molecular targeting by gene therapy approaches a feasible therapeutic strategy. Although gene therapy was originally designed to correct single gene defects, it has now evolved to encompass all forms of therapeutic interventions involving engineered cells and nucleic acids that modify the overall pattern of gene expression within target tissues. Several preclinical studies and clinical trials have tested the efficacy of targeting specific molecules in patients with HNSCC, using genetic therapy approaches. This review discusses promising preclinical and clinical approaches and new directions for HNSCC gene therapy.

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“…Injection of alloantigen into tumors to induce expression of a foreign class I major histocompatibility complex protein (HLA-B7) has been used in a phase I trial on 9 patients with recurrent and refractory head and neck SCC. There were 4 partial responses and no toxicity [42].…”

Section: Strategies Based On Cytogenetic Changesmentioning

confidence: 92%

The Treatment of Distant Metastases in Head and Neck Cancer – Present and Future

Buckley

Ferlito

Shaha

et al. 2001

ORL

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At the present time the occurrence of distant metastases in patients with head and neck squamous cell carcinoma means that lifespan is measured in months. In most instances treatment is purely palliative. Isolated lung metastasis can be successfully removed with long-term disease control in selected patients. Radiotherapy can be useful for palliation of bone metastases and occasionally lung or brain metastases. Chemotherapy does not have a major impact at the present time except for the treatment of metastases from nasopharyngeal cancer. Palliative symptomatic care, along with appropriate pain control, is essential since pain management is very important in these patients. A significant change in the survival of patients with head and neck cancer is only likely to occur by the development of new approaches to treatment. Blocking tumor angiogenesis and treatment based on genetic abnormalities or cell surface receptors offer the two strategies that are most likely to be successful.

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Alloantigen Gene Therapy for Squamous Cell Carcinoma of the Head and Neck

Abstract: These data demonstrate the potential efficacy and lack of toxicity of this form of alloantigen gene therapy. A multi-institutional study has been initiated to expand on these findings.

Cited by 39 publications

References 28 publications

Tissue distribution of liposome-mediated epidermal growth factor receptor antisense gene therapy

Tissue distribution of liposome-mediated epidermal growth factor receptor antisense gene therapy

The Current State of Head and Neck Cancer Gene Therapy

The Treatment of Distant Metastases in Head and Neck Cancer – Present and Future

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