A Combination of flk1-Based DNA Vaccine and an Immunomodulatory Gene (IL-12) in the Treatment of Murine Cancer

Feng, Keke; Zhao, Hongyang; Qiu, Hui; Liu, Jixiao; Chen, Jian

doi:10.1089/cbr.2004.19.649

Cited by 10 publications

(5 citation statements)

References 24 publications

(22 reference statements)

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“…Our results are supported by the findings that the therapy of attenuated Salmonella typhimurium vaccine strain encoding murine VEGF combined with the IL-12 gene has a significant effect against tumors by facilitating apoptosis (27). As mentioned earlier, the induction of cell cycle arrest was found to be related with the apoptosis of tumor tissue in our study.…”

Section: Discussionsupporting

confidence: 91%

Mannosylated chitosan nanoparticle–based cytokine gene therapy suppressed cancer growth in BALB/c mice bearing CT-26 carcinoma cells

Kim

Jin²,

Kim³

et al. 2006

Molecular Cancer Therapeutics

138

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Cancer immunotherapy relies on the ability of the immune system to destroy tumor cells selectively and to elicit a long-lasting memory of such activity. is an immunomodulatory cytokine produced primarily by antigen-presenting cells, which play an important role in promoting Th1-type immune response and cell-mediated immunity. To augment the antitumor immune action by in vivo IL-12 gene delivery, mannosylated chitosan (MC) was prepared to induce mannose receptor -mediated endocytosis of IL-12 gene directly into dendritic cells which reside within the tumor. Upon characterization, MC was proven to be suitable for IL-12 gene delivery due to good physicochemical properties and low cytotoxicity. In addition, MC exhibited much enhanced IL-12 gene transfer efficiency to dendritic cells rather than chitosan itself in terms of the induction of murine IL-12 p70 and murine IFN-;. In animal studies, intratumoral injection of MC/ plasmid encoding murine IL-12 complex into BALB/c mice bearing CT-26 carcinoma cells clearly suppressed tumor growth and angiogenesis, and significantly induced cell cycle arrest and apoptosis. Therefore, this study provides a new MC-mediated cytokine gene delivery system for cancer immunotherapy.

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Section: Discussionsupporting

confidence: 91%

Mannosylated chitosan nanoparticle–based cytokine gene therapy suppressed cancer growth in BALB/c mice bearing CT-26 carcinoma cells

Kim

Jin²,

Kim³

et al. 2006

Molecular Cancer Therapeutics

138

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“…Gene therapy studies, involving tumor modification for production of inflammatory cytokines (e.g. IL-2) to enhance tumor immunogenicity [78] as well as with IL-12-expressing DNA plasmids to slow tumor growth and stimulate a robust CTL response, [79] have also utilized the GL261 model.…”

Section: Gl261; C57bl/6 Modelmentioning

confidence: 99%

Immunocompetent murine models for the study of glioblastoma immunotherapy

Fakurnejad

Sayegh

et al. 2014

Journal of Translational Medicine

183

185

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Glioblastoma remains a lethal diagnosis with a 5-year survival rate of less than 10%. (NEJM 352:987-96, 2005) Although immunotherapy-based approaches are capable of inducing detectable immune responses against tumor-specific antigens, improvements in clinical outcomes are modest, in no small part due to tumor-induced immunosuppressive mechanisms that promote immune escape and immuno-resistance. Immunotherapeutic strategies aimed at bolstering the immune response while neutralizing immunosuppression will play a critical role in improving treatment outcomes for glioblastoma patients. In vivo murine models of glioma provide an invaluable resource to achieving that end, and their use is an essential part of the preclinical workup for novel therapeutics that need to be tested in animal models prior to testing experimental therapies in patients. In this article, we review five contemporary immunocompetent mouse models, GL261 (C57BL/6), GL26 (C57BL/6) CT-2A (C57BL/6), SMA-560 (VM/Dk), and 4C8 (B6D2F1), each of which offer a suitable platform for testing novel immunotherapeutic approaches.

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“…[12][13][14][15] These combinations demonstrate enhanced efficacy with reduced toxicity as the levels of both components are reduced and these both factors are required for an effective therapy in renal cell carcinoma.…”

Section: Resultsmentioning

confidence: 99%

Non-viral delivery of interleukin-2 and soluble Flk-1 inhibits metastatic and primary tumor growth in renal cell carcinoma

et al. 2007

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Treatments for renal cell carcinoma, while promising, are still limited by toxicity and cost. In the hopes of finding a novel compound or combination, we developed a plasmid containing the genes for interleukin-2 (IL-2) and soluble vascular endothelial growth factor receptor 2 (msFlk1). The plasmid, p2CMVIL2/msFlk1, demonstrated similar in vitro transgene expression of IL-2 or msFlk1 compared to their single-agent counterparts. Subcutaneous tumor growth was significantly inhibited in the p2CMVIL2/msFlk1 group when delivered locally by the non-viral water soluble polymer, WSLP and exhibited a 50% increase in survival over glucose and single-agent controls. In vivo experimentation demonstrated that WSLP/msFlk1 decreased microvessel density in pCMVmsFlk1 and p2CMVIL2/msFlk1 treated groups. Furthermore, tumor-infiltrating lymphocytes expressing CD45RO and CD68 were increased within the tumor microenvironment upon p2CMVIL2/msFlk1 treatment. To determine the effects of p2CMVIL2/msFlk1 in an experimental RENCA lung metastases model, therapeutic DNA was delivered systemically following complexation with the angiogenic endothelial-targeting polymer PEI-g-PEG-RGD. The p2CMVIL2/msFlk1 treatment significantly reduced metastases by 56% over single-agent therapy and increased survival proportions by 50% over all groups. Our work clearly demonstrates that non-viral delivery of p2CMVIL2/msFlk1 can inhibit RENCA growth in a synergistic manner and may represent a new treatment for renal carcinoma.

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A Combination of flk1-Based DNA Vaccine and an Immunomodulatory Gene (IL-12) in the Treatment of Murine Cancer

Abstract: The therapy of attenuated Salmonella typhimurium vaccine strain encoding flk1 combined with the interleukin-12 gene has significant synergistic effect against tumors.

Cited by 10 publications

References 24 publications

Mannosylated chitosan nanoparticle–based cytokine gene therapy suppressed cancer growth in BALB/c mice bearing CT-26 carcinoma cells

Mannosylated chitosan nanoparticle–based cytokine gene therapy suppressed cancer growth in BALB/c mice bearing CT-26 carcinoma cells

Immunocompetent murine models for the study of glioblastoma immunotherapy

Non-viral delivery of interleukin-2 and soluble Flk-1 inhibits metastatic and primary tumor growth in renal cell carcinoma

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