Dosimetric and technical considerations for interstitial adenoviral gene therapy as applied to prostate cancer

Li, Shidong; Simons, J.W.; Detorie, Nicholas; O’Rourke, Brian; Hamper, Ulrike M.; DeWeese, Theodore L.

doi:10.1016/s0360-3016(02)03862-2

Cited by 14 publications

(6 citation statements)

References 26 publications

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“…Theoretically, each track would form a cylinder with a 1-cm 2 cross-sectional area using this injection technique. This protocol is similar in concept to that previously reported by Li et al (17).…”

Section: Gene Injectionssupporting

confidence: 71%

A phase I trial of hyperthermia-induced interleukin-12 gene therapy in spontaneously arising feline soft tissue sarcomas

Siddiqui¹,

LaRue³

et al. 2007

Molecular Cancer Therapeutics

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Interleukin-12 (IL-12), a proinflammatory cytokine, shows anticancer properties. Systemically administered IL-12 causes dose-dependent toxicity. To achieve localized intratumoral gene expression, an adenoviral gene therapy vector with IL-12 controlled by a heat-inducible promoter (heat shock promoter 70B) was developed and tested in a phase I clinical trial in cats with spontaneously arising soft tissue sarcoma. A feasibility study was done in 16 cats with soft tissue sarcoma using murine IL-12 and/or enhanced green fluorescent protein adenoviral vectors under cytomegalovirus or heat shock promoter 70 control. Subsequently, we conducted a phase I clinical trial using an adenoviral feline IL-12 construct in 13 cats with soft tissue sarcoma. The soft tissue sarcomas were irradiated (48 Gy/16 fractions) followed by intratumoral injection of adenovirus. Twenty-four hours postinjection, tumors were heated (41°C, 60 min). Tumor expression of feline IL-12 and IFN-; was determined. Cats were monitored for systemic toxicity. For the murine IL-12 construct, an association was noted between viral dose and murine IL-12 levels within tumor, whereas serum levels were minimal. Mild toxicity was noted at 10 11 plaque-forming units (pfu). With the feline IL-12 construct, high levels of feline IL-12 mRNA were detected in tumor biopsies with low or absent IFN-; mRNA following gene therapy. Hematologic and hepatic toxicities were noted at the highest viral doses and were associated with detection of IFN-; mRNA in tumor. It is possible to localize gene expression and limit systemic toxicity of IL-12 using the hyperthermia-induced gene therapy approach. The maximum tolerated dose of the feline IL-12 adenoviral vector was 10

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Section: Gene Injectionssupporting

confidence: 71%

A phase I trial of hyperthermia-induced interleukin-12 gene therapy in spontaneously arising feline soft tissue sarcomas

Siddiqui¹,

LaRue³

et al. 2007

Molecular Cancer Therapeutics

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“…Gene therapy for cancer involves the introduction of immunostimulatory molecules ex vivo or in vivo into cancer cells. Gene therapy has been used extensively for the treatment of prostate, head and neck, and colorectal cancer . However, it has failed in clinical trials due to the difficulty in establishing primary tumor cells .…”

Section: Immunotherapeutic Approaches For Cancer Treatmentmentioning

confidence: 99%

“…Gene therapy has been used extensively for the treatment of prostate, head and neck, and colorectal cancer. [130][131][132] However, it has failed in clinical trials due to the difficulty in establishing primary tumor cells. 12,13 Currently, viral and nonviral vector-based gene delivery systems are being used and are associated with substantial limitations.…”

Section: Gene Therapy-based Vaccines For Cancer Treatmentmentioning

confidence: 99%

Immunotherapeutic strategies for cancer treatment: A novel protein transfer approach for cancer vaccine development

Shashidharamurthy

Bozeman

Patel

et al. 2011

Medicinal Research Reviews

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Cancer cells have developed numerous ways to escape immune surveillance and gain unlimited proliferative capacity. Currently, several chemotherapeutic agents and radiotherapy, either alone or in combination, are being used to treat malignancies. However, both of these therapies are associated with several limitations and detrimental side effects. Therefore, recent scientific investigations suggest that immunotherapy is among the most promising new approaches in modern cancer therapy. The focus of cancer immunotherapy is to boost both acquired and innate immunity against malignancies by specifically targeting tumor cells, and leaving healthy cells and tissues unharmed. Cellular, cytokine, gene, and monoclonal antibody therapies have progressively become promising immunotherapeutic approaches that are being tested for several cancers in preclinical models as well as in the clinic. In this review, we discuss recent advances in these immunotherapeutic approaches, focusing on new strategies that allow the expression of specific immunostimulatory molecules on the surface of tumor cells to induce robust antitumor immunity.

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“…It has recently been reported that adenovirus-mediated gene transfer of the p53 upregulated modulator of apoptosis (PUMA) gene can efficiently and specifically target human breast cancer cells and enhance their radiosensitivity (69). Despite use in clinical trials for the treatment of head and neck cancer (70), prostate cancer (71) and colorectal cancer (72), adenovirus vectors are highly immunogenic (73, 74) which poses a potential health risk to the patient. These vectors typically activate the innate immune system and in doing so can mediate unwanted inflammatory responses.…”

Section: Current Immunotherapiesmentioning

confidence: 99%

Cancer vaccine development: Designing tumor cells for greater immunogenicity

Bozeman

Shashidharamurthy²,

Paulos³

et al. 2010

Front Biosci

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Cancer vaccine development is one of the most hopeful and exhilarating areas in cancer research. For this reason, there has been a growing interest in the development and application of novel immunotherapies for the treatment of cancer with the focus being on stimulating the immune system to target tumor cells specifically while leaving normal cells unharmed. From such research has emerged a host of promising immunotherapies such as dendritic cell-based vaccines, cytokine therapies and gene transfer technology. These therapies seek to counteract the poor immunogenicity of tumors by augmenting the host’s immune system with a variety of immunostimulatory proteins such as cytokines and costimulatory molecules. While such therapies have proven effective in the induction of anti-tumor immunity in animal models, they are less than optimal and pose a high risk of clinical infeasibility. Herein, we further discuss these immunotherapies as well as a feasible and efficient alternative that, in pre-clinical animal models, allows for the expression of specific immunostimulatory molecules on the surface of tumor cells by a novel protein transfer technology.

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Dosimetric and technical considerations for interstitial adenoviral gene therapy as applied to prostate cancer

Cited by 14 publications

References 26 publications

A phase I trial of hyperthermia-induced interleukin-12 gene therapy in spontaneously arising feline soft tissue sarcomas

A phase I trial of hyperthermia-induced interleukin-12 gene therapy in spontaneously arising feline soft tissue sarcomas

Immunotherapeutic strategies for cancer treatment: A novel protein transfer approach for cancer vaccine development

Cancer vaccine development: Designing tumor cells for greater immunogenicity

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