LATHEY JL, MATIJEVIC M, KLENCKE B, PALEFSKY J, URBAN RG, HEDLEY ML; Interscience Conference on Antimicrobial Agents and Chemotherapy (41st : 2001 : Chicago, Ill.).
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2001 Dec 16-19; 41: abstract no. G-1564.
ZYCOS, Lexington, MA
BACKGROUND: A dose escalation, phase I/II trial was conducted in HPV positive patients with high-grade anal dysplasia (ASIL) to test the safety of a microsphere encapsulated DNA vaccine candidate (ZYC101). The vaccine expresses multiple HLA-A2 restricted CTL epitopes derived from the HPV type 16 E7 protein. METHODS: Twelve male patients who are both HPV type 16 and HLA-A2 positive were given 4 intramuscular injections 3 weeks apart. Patient peripheral blood mononuclear cells (PBMC) were isolated and frozen at each of 6 clinical visits covering 24 weeks. Elispot assays were set-up on PBMC to enumerate interferon gamma (IFNg) producing cells in the first nine patients. Three CTL epitopes, 2.1, 2.4, and 2.4C, which were contained in the vaccine, were used to test for response to immunization. RESULTS: There were significant increases in IFNg producing cells in response to all three HPV CTL epitopes: (Median, Entry vs Week 24, paired T test) 2.1, 48 vs 497, p=0.004; 2.4, 1 vs 245, p=0.01; 2.4C, 18 vs 435, p=0.004. The evaluation of individual responses showed that 8/9, 7/9, and 6/9 individuals had significant increases (> 95% confidence interval of variability in negative controls) in the number of IFNg positive cells for 1, 2, or 3 HPV peptides, respectively. The first positive response was at 3 weeks following the first injection. PBMC from 6 of these patients were retested by Elispot following expansion and antigen restimulation in vitro for 24 days. All 6 patients, including the initial nonresponder, demonstrated positive increases in the number of HPV-specific IFNg positive cells by expanded Elispot. CONCLUSION: Thus, immunization with a microsphere encapsulated DNA vaccine (ZYC101) that expresses multiple HLA-A2 restricted CTL epitopes derived from the HPV type 16 E7 protein stimulated an HPV specific immune response in all 9 patients evaluated.
Publication Types:
Keywords:
- Epitopes
- HLA-A2 Antigen
- Humans
- Immunization
- In Vitro
- Male
- Oncogene Proteins, Viral
- Papillomaviridae
- T-Lymphocytes, Cytotoxic
- Vaccines, DNA
- immunology
- methods
- oncogene protein E7, Human papillomavirus type 16
Other ID:
UI: 102270647
From Meeting Abstracts