| Autor: |
Klencke B; Department of Medicine, Division of Medical Oncology, University of California at San Francisco, 94115, USA. klenckeb@medicine.ucsf.edu, Matijevic M, Urban RG, Lathey JL, Hedley ML, Berry M, Thatcher J, Weinberg V, Wilson J, Darragh T, Jay N, Da Costa M, Palefsky JM |
| Jazyk: |
angličtina |
| Zdroj: |
Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2002 May; Vol. 8 (5), pp. 1028-37. |
| Abstrakt: |
High-grade dysplasia induced by high-risk types of human papillomavirus (HPV) precedes invasive cancer in anal squamous epithelium just as it does in the cervix. A therapeutic HPV vaccine strategy as a potential treatment for anal dysplasia was tested in a standard Phase I dose escalation trial. The primary objective was to evaluate the safety of the agent; additional study aims were to evaluate the histological response, immune response, and effect on anal HPV-16 infection. Each subject was treated with four i.m. injections of 50-400 microg of ZYC101 at 3-week intervals. ZYC101 is composed of plasmid DNA encapsulated in biodegradable polymer microparticles. The plasmid DNA encodes for multiple HLA-A2-restricted epitopes derived from the HPV-16 E7 protein, one of two HPV oncoproteins consistently expressed in neoplastic cells. Fifty-six potential anal dysplasia subjects were screened to identify 12 eligible subjects with HPV-16 anal infection and a HLA-A2 haplotype. The investigational agent was well tolerated in all subjects at all dose levels tested. Three subjects experienced partial histological responses, including one of three subjects receiving the 200-microg dose and two subjects at the 400-microg dose level. Using a direct Elispot, 10 of 12 subjects demonstrated increased immune response to the peptide epitopes encoded within ZYC101; each continued to show elevated immune responses 6 months after the initiation of therapy. These results support the continued investigation of a therapeutic vaccination strategy for anal dysplasia. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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