Phase I Study of a Plasmid DNA Vaccine Encoding MART-1 in Patients with Resected Melanoma at Risk for Relapse
| Autor: | Ronda Carlisle, Robert M. Conry, Wayne Aldrich, Pierre L. Triozzi, Albert F. LoBuglio, Karen O. Allen |
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| Rok vydání: | 2005 |
| Předmět: |
Adult
Male Cancer Research HBsAg medicine.medical_treatment Immunology Lymphocyte Activation Interferon-gamma Mice MART-1 Antigen Plasmid Species Specificity Melanocyte differentiation Antigen Antigens Neoplasm Vaccines DNA Animals Humans Immunology and Allergy Medicine Melanoma Aged Cell Proliferation Pharmacology Immunity Cellular Mice Inbred BALB C Hepatitis B Surface Antigens biology business.industry ELISPOT Vaccination Immunotherapy Middle Aged Neoplasm Proteins Mice Inbred C57BL Antibody Formation Leukocytes Mononuclear biology.protein Female Neoplasm Recurrence Local Antibody business Lymphoproliferative response Plasmids |
| Zdroj: | Journal of Immunotherapy. 28:382-388 |
| ISSN: | 1524-9557 |
| Popis: | Immunization with plasmid DNA represents an attractive method for increasing cellular immune responses against cancer antigens. The safety and immunologic response of a plasmid encoding the MART-1 melanocyte differentiation antigen was evaluated in 12 patients with resected melanoma at risk for relapse. As a control, patients were also administered a plasmid encoding hepatitis B surface antigen (HBsAg). After establishing immunologic activity of the vaccines in mice, groups of three to six HLA-A2-positive patients were enrolled into one of three cohorts in which they received intramuscular injections of the MART-1 plasmid into the right deltoid and the HBsAg plasmid into the left deltoid at doses of 0.1, 0.3, or 1.0 mg on days 1, 43, 85, and 127. Injections were well tolerated. Toxicity was limited to grade 1 pain and injection site tenderness. Systemic toxicity was not observed. Although baseline MART-1-specific lymphoproliferative and ELISPOT responses were evident, no patient manifested increases after injection of the MART-1 plasmid. Furthermore, changes in MART-1-specific precursors were not evident after immunization as assessed by an in vitro stimulation assay. No patients manifested a lymphoproliferative response to HBsAg antigen, and significant antibody responses to HBsAg were also not observed. Although injections were safe, the authors could not show significant immunologic responses to plasmid encoding MART-1 or HBsAg using the dose, schedule, and route of administration applied. This study underscores species differences in the ability to respond to plasmid immunogens. |
| Databáze: | OpenAIRE |
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