Pyrogenicity of human adenoviruses

Kato, Naoya

doi:10.1099/0022-1317-81-11-2611

Cited by 5 publications

References 31 publications

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Intratumoral Adenovirus-Mediated Suicide Gene Transfer for Hepatic Metastases from Colorectal Adenocarcinoma: Results of a Phase I Clinical Trial

et al. 2001

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Animal studies have shown that direct injection of an adenoviral vector (Adv.RSV-tk) expressing the herpes thymidine kinase gene into established tumors in the liver, followed by systemic ganciclovir administration, was effective in inducing tumor necrosis. Toxicities were minimal at therapeutically effective vector doses, although severe hepatic necroinflammation was seen at much higher supratherapeutic doses. We conducted a clinical phase I trial in patients with metastatic colorectal adenocarcinoma in the liver to assess the safety of intratumoral Adv.RSV-tk injection (escalating doses) followed by intravenous ganciclovir (fixed dose). The vector was injected into a metastatic tumor in the liver under local anesthesia by percutaneous needle placement with concurrent ultrasonographic monitoring to prevent injection or leakage into adjacent normal liver structures. We treated 16 patients in five dose level cohorts of Adv.RSV-tk, from 1.0x10(10) to 1.0x10(13) virus particles per patient. Hepatic toxicities were low, with transient grade 1 elevations in serum aminotransferase levels in 3 of 16 patients. Other toxicities were also transient: grade 2-3 fevers in 5 of 16 patients, grade 3 thrombocytopenia in 1 of 16 patients, and grade 2 leucopenia in 3 of 16 patients. These results indicate that Adv.RSV-tk can be safely administered by percutaneous intratumoral injection in patients with hepatic metastases at doses up to 1.0x10(13) virus particles per patient, and can provide the basis for future clinical trials involving intratumoral adenoviral vector injection.

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Intratumoral Adenovirus-Mediated Suicide Gene Transfer for Hepatic Metastases from Colorectal Adenocarcinoma: Results of a Phase I Clinical Trial

et al. 2001

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Adenovirus Vector Toxicity

Harmon

Byrnes

2017

Safety and Efficacy of Gene-Based Therapeutics for Inherited Disorders

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Intratumoral Delivery of Adenovirus-Mediated Interleukin-12 Gene in Mice with Metastatic Cancer in the Liver

et al. 2002

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Clinical trials of recombinant human interleukin-12 (rhIL-12) delivered by intravenous administration have shown dose-limiting toxicities with limited tumor responses at the doses tested. We have previously reported that intratumoral injection of an adenovirus vector expressing murine interleukin-12 (Adv.RSV-mIL-12) was effective in inducing antitumor immune responses, tumor regression, and long-term survival in mice with established metastatic cancer in the liver. We now report additional studies in the same murine tumor model to assess the safety of intratumoral Adv.RSV-mIL-12 injection. At vector doses that were previously shown to be therapeutically effective, no inflammation in the liver or lungs, and no significant elevations in serum creatinine and aminotransferases were seen after vector injection. Serum elevations of IL-12 and interferon-gamma (IFN-gamma) were 17- and 19-fold lower than peak levels after intravenous recombinant IL-12 at the maximal tolerated dose in clinical trials. No elevations in serum proinflammatory cytokines (interleukin-6, tumor necrosis factor-alpha) were noted up to 2 weeks after vector injection. No systemic dissemination of the vector was detected on polymerase chain reaction (PCR) assays at therapeutically effective vector doses. At higher supratherapeutic vector doses of Adv.RSV-mIL-12, however, inflammation in the liver and lungs with elevation in serum aminotransferases were seen, but not in controls injected with the equivalent particle number of an empty adenoviral vector. These results support the cautious testing in patients with hepatic metastases of adenovirus mediated IL-12 gene delivery by intratumoral injection.

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Pyrogenicity of human adenoviruses

Cited by 5 publications

References 31 publications

Intratumoral Adenovirus-Mediated Suicide Gene Transfer for Hepatic Metastases from Colorectal Adenocarcinoma: Results of a Phase I Clinical Trial

Intratumoral Adenovirus-Mediated Suicide Gene Transfer for Hepatic Metastases from Colorectal Adenocarcinoma: Results of a Phase I Clinical Trial

Adenovirus Vector Toxicity

Intratumoral Delivery of Adenovirus-Mediated Interleukin-12 Gene in Mice with Metastatic Cancer in the Liver

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