Biological activities of a recombinant adenovirus p53 (SCH 58500) administered by hepatic arterial infusion in a Phase 1 colorectal cancer trial
| Autor: | Stephen R. Indelicato, Shu Fen Wen, Jeremy Shinoda, I A Atencio, Alan P. Venook, Daniel C. Maneval, Mary Lynn Musco, Robert S. Warren, Beth Hutchins, Ronald Bordens, Grace Michael, M Fritz, Karen Kolz, Sheila Jacobs, Jo Ann Horowitz |
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| Rok vydání: | 2005 |
| Předmět: |
Adult
Male Cancer Research medicine.medical_treatment Genetic Vectors Apoptosis Pharmacology Biology Antibodies Viral Adenoviridae Proinflammatory cytokine Hepatic Artery Hepatic arterial infusion medicine Humans Infusions Intra-Arterial Receptor Molecular Biology Aged DNA Primers Analysis of Variance Reverse Transcriptase Polymerase Chain Reaction Liver Neoplasms Antibody titer Genetic Therapy Middle Aged Genes p53 Recombinant Adenovirus-p53 SCH-58500 Laser Scanning Cytometry Cytokine Immunology biology.protein Cytokines Receptors Virus Molecular Medicine Female Antibody Colorectal Neoplasms |
| Zdroj: | Cancer Gene Therapy. 13:169-181 |
| ISSN: | 1476-5500 0929-1903 |
| DOI: | 10.1038/sj.cgt.7700870 |
| Popis: | The major focus of intrahepatic arterial (IHA) administration of adenoviruses (Ad) has been on safety. Currently, there is little published data on the biological responses to Ad when administered via this route. As part of a Phase I study, we evaluated biological responses to a replication-defective adenovirus encoding the p53 transgene (SCH 58500) when administered by hepatic arterial infusion to patients with primarily colorectal cancer metastatic to the liver. In analyzing biological responses to the Ad vector, we found that both total and neutralizing Ad antibodies increased weeks after SCH 58500 infusion. The fold increase in antibody titers was not dependent on SCH 58500 dosage. The proinflammatory cytokine interleukin-6 (IL-6) transiently peaked within 6 h of dosing. The cytokine sTNF-R2 showed elevation by 24 h post-treatment, and fold increases were directly related to SCH 58500 doses. Cytokines TNF-alpha, IL-1beta, and sTNF-R1 showed no increased levels over 24 h. Predose antibody levels did not appear to predict transduction, nor did serum Ad neutralizing factor (SNF). Delivery of SCH 58500 to tumor tissue occurred, though we found distribution more predominantly in liver tissues, as opposed to tumors. RT-PCR showed significantly higher expression levels (P |
| Databáze: | OpenAIRE |
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