Phase I immunotherapeutic trial with long peptides spanning the E6 and E7 sequences of high-risk human papillomavirus 16 in end-stage cervical cancer patients shows low toxicity and robust immunogenicity - PubMed (original) (raw)
Clinical Trial
. 2008 Jan 1;14(1):169-77.
doi: 10.1158/1078-0432.CCR-07-1881.
Marij J P Welters, A Rob P M Valentijn, Margriet J G Lowik, Dorien M A Berends-van der Meer, Annelies P G Vloon, Jan W Drijfhout, Amon R Wafelman, Jaap Oostendorp, Gert Jan Fleuren, Rienk Offringa, Sjoerd H van der Burg, Cornelis J M Melief
Affiliations
- PMID: 18172268
- DOI: 10.1158/1078-0432.CCR-07-1881
Free article
Clinical Trial
Phase I immunotherapeutic trial with long peptides spanning the E6 and E7 sequences of high-risk human papillomavirus 16 in end-stage cervical cancer patients shows low toxicity and robust immunogenicity
Gemma G Kenter et al. Clin Cancer Res. 2008.
Free article
Abstract
Purpose: To determine the toxicity, safety, and immunogenicity of a human papillomavirus 16 (HPV16) E6 and E7 long peptide vaccine administered to end-stage cervical cancer patients.
Experimental design: Three groups of end-stage cervical cancer patients (in total n = 35) were s.c. vaccinated with HPV16 E6 combined with or separated from HPV16 E7 overlapping long peptides in Montanide ISA-51 adjuvant, four times at 3-week intervals. Group 1 received 300 microg/peptide at a single site and group 2 received 100 microg/peptide of the E6 peptides in one limb and 300 microg/peptide of the E7 peptides in a second limb. Group 3 received separate injections of E6 and E7 peptides, each at a dose of 50 microg/peptide. The primary end point was to determine safety and toxicity of the HPV16 long peptides vaccine. In addition, the vaccine-induced T-cell response was assessed by IFN gamma enzyme-linked immunospot.
Results: No toxicity beyond grade 2 was observed during and after four vaccinations. In a few patients, transient flu-like symptoms were observed. Enzyme-linked immunospot analysis of the vaccine-induced immune response revealed that coinjection of the E6 and E7 peptides resulted in a strong and broad T-cell response dominated by immunity against E6. Injection of the E6 and E7 peptides at two different sites increased the E7 response but did not affect the magnitude of the E6-induced immune response.
Conclusions: The HPV16 E6 and E7 long peptide-based vaccine is well tolerated and capable of inducing a broad IFN gamma-associated T-cell response even in end-stage cervical cancer patients.
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