Immunotherapy of Advanced Malignancy by Direct Gene Transfer of an Interleukin-2 DNA/DMRIE/DOPE Lipid Complex: Phase I/II Experience

Galanis, Evanthia; Hersh, Evan M.; Stopeck, Alison; González, Rodrigo; Burch, Patrick A.; Spier, Catherine M.; Akporiaye, Emmanuel T.; Rinehart, John J.; Edmonson, John H.; Sobol, Robert E.; Forscher, Charles; Sondak, Vernon K.; Lewis, Bradley D.; Unger, Evan C.; OʼDriscoll, Michael; Selk, Linda; Rubin, Joshua T.

doi:10.1200/jco.1999.17.10.3313

Cited by 95 publications

(46 citation statements)

References 24 publications

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“…route. 14,22 A phase I trial in cancer patients with lung metastases confirmed intratumoral replication of the virus in lung metastases, 22 therefore, indicating that the first passage of the virus through the lungs after i.v. administration can be exploited to target viral delivery.…”

Section: Discussionmentioning

confidence: 99%

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Phase I–II trial of ONYX-015 in combination with MAP chemotherapy in patients with advanced sarcomas

et al. 2005

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Section: Discussionmentioning

confidence: 99%

“…ONYX-015 in combination with MAP chemotherapy in sarcomas E Galanis et al administration of the IL-2 gene, 22 focusing on an immunotherapeutic approach.…”

Section: Discussionmentioning

confidence: 99%

Phase I–II trial of ONYX-015 in combination with MAP chemotherapy in patients with advanced sarcomas

et al. 2005

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“…To address these problems, nonviral vectors, including cationic lipids or polycationic polymers, are attractive candidates because of their low immunogenicity, relative safety, and low cost. Direct intratumoral injection of IL-2 DNA/cationic lipid complex has been shown to be safe and efficient in patients with metastatic melanoma or metastatic renal cell carcinoma in clinical trials (13,14). However, the efficiency of these nonviral vectors for IL-2 gene delivery was lower than that of rAdv-IL-2.…”

Section: Introductionmentioning

confidence: 88%

Effective Melanoma Immunotherapy with Interleukin-2 Delivered by a Novel Polymeric Nanoparticle

Yao

Huo

et al. 2011

Molecular Cancer Therapeutics

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Interleukin-2 (IL-2) has been shown to possess antitumor activity in numerous preclinical and clinical studies. However, the short half-life of recombinant IL-2 protein in serum requires repeated high-dose injections, resulting in severe side effects. Although adenovirus-mediated IL-2 gene therapy has shown antitumor efficacy, the host antibody response to adenoviral particles and potential biosafety concerns still obstruct its clinical applications. Here we report a novel nanopolymer for IL-2 delivery, consisting of low molecular weight polyethylenimine (600Da) linked by b-cyclodextrin and conjugated with folate (named H1). H1 was mixed with IL-2 plasmid to form H1/pIL-2 polyplexes of around 100 nm in diameter. Peritumoral injection of these polyplexes suppressed the tumor growth and prolonged the survival of C57/BL6 mice bearing B16-F1 melanoma grafts. Importantly, the antitumor effects of H1/pIL-2 (50 mg DNA) were similar to those of recombinant adenoviruses expressing IL-2 (rAdv-IL-2; 2 Â 10 8 pfu). Furthermore, we showed that H1/pIL-2 stimulated the activation and proliferation of CD8þ, CD4þ T cell, and natural killer cells in peripheral blood and increased the infiltration of CD8þ, CD4þ Tcells, and natural killer cells into the tumor environment. In conclusion, these results show that H1/pIL-2 is an effective and safe melanoma therapeutic with an efficacy comparable to that of rAdv-IL-2. This treatment represents an alternative gene therapy strategy for melanoma. Mol Cancer Ther; 10(6); 1082-92. Ó2011 AACR.

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“…CD8 + T cells were found to be the primary effectors, while CD4 + T cells did not appear to play a significant role in the development of tumor-specific immunity. In a phase I study followed by three phase I/II studies, RCC, melanoma, and sarcoma patients were treated with various concentrations of Leuvectin (Vical Inc., San Diego, CA) given once or twice weekly over 3 to 6 weeks [33]. Leuvectin contains a plasmid encoding human IL-2 formulated with the cationic lipid DMRIE/DOPE.…”

Section: Cytokine-based Immune Manipulationmentioning

confidence: 99%

Immune gene therapy in urology

et al. 2002

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Effective treatments are needed urgently for metastatic disease in bladder, prostate, and renal cell cancer. In the past few years, several new approaches for treating these conditions have been proposed, including gene therapy. A number of different strategies have been developed to accomplish urologic cancer gene therapy. Genetic immunomodulation strategies attempt to activate immune defense mechanisms against tumor cells by transfer of tumor antigens, cytokine genes, or strongly immunogenic cell surface molecules. In this review, we illustrate the recent developments in immune gene therapy.

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Immunotherapy of Advanced Malignancy by Direct Gene Transfer of an Interleukin-2 DNA/DMRIE/DOPE Lipid Complex: Phase I/II Experience

Abstract: Direct intratumoral injection of Leuvectin is a safe and possibly effective immunotherapeutic approach in the treatment of certain tumor types.

Cited by 95 publications

References 24 publications

Phase I–II trial of ONYX-015 in combination with MAP chemotherapy in patients with advanced sarcomas

Phase I–II trial of ONYX-015 in combination with MAP chemotherapy in patients with advanced sarcomas

Effective Melanoma Immunotherapy with Interleukin-2 Delivered by a Novel Polymeric Nanoparticle

Immune gene therapy in urology

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