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27.04.2017 | Original Article

HPV16 E7 DNA tattooing: safety, immunogenicity, and clinical response in patients with HPV-positive vulvar intraepithelial neoplasia

verfasst von: Sanne Samuels, A. Marijne Heeren, Henry J. M. A. A. Zijlmans, Marij J. P. Welters, Joost H. van den Berg, Daisy Philips, Pia Kvistborg, Ilina Ehsan, Suzy M. E. Scholl, Bastiaan Nuijen, Ton N. M. Schumacher, Marc van Beurden, Ekaterina S. Jordanova, John B. A. G. Haanen, Sjoerd H. van der Burg, Gemma G. Kenter

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 9/2017

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Abstract

Background

Usual type vulvar intraepithelial neoplasia (uVIN) is caused by HPV, predominantly type 16. Several forms of HPV immunotherapy have been studied, however, clinical results could be improved. A novel intradermal administration route, termed DNA tattooing, is superior in animal models, and was tested for the first time in humans with a HPV16 E7 DNA vaccine (TTFC-E7SH).

Methods

The trial was designed to test safety, immunogenicity, and clinical response of TTFC-E7SH in twelve HPV16⁺ uVIN patients. Patients received six vaccinations via DNA tattooing. The first six patients received 0.2 mg TTFC-E7SH and the next six 2 mg TTFC-E7SH. Vaccine-specific T-cell immunity was evaluated by IFNγ-ELISPOT and multiparametric flow cytometry.

Results

Only grade I-II adverse events were observed upon TTFC-E7SH vaccination. The ELISPOT analysis showed in 4/12 patients a response to the peptide pool containing shuffled E7 peptides. Multiparametric flow cytometry showed low CD4⁺ and/or CD8⁺ T-cell responses as measured by increased expression of PD-1 (4/12 in both), CTLA-4 (2/12 and 3/12), CD107a (5/12 and 4/12), or the production of IFNγ (2/12 and 1/12), IL-2 (3/12 and 4/12), TNFα (2/12 and 1/12), and MIP1β (3/12 and 6/12). At 3 months follow-up, no clinical response was observed in any of the twelve vaccinated patients.

Conclusion

DNA tattoo vaccination was shown to be safe. A low vaccine-induced immune response and no clinical response were observed in uVIN patients after TTFC-E7SH DNA tattoo vaccination. Therefore, a new phase I/II trial with an improved DNA vaccine format is currently in development for patients with uVIN.

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Titel: HPV16 E7 DNA tattooing: safety, immunogenicity, and clinical response in patients with HPV-positive vulvar intraepithelial neoplasia
verfasst von: Sanne Samuels
A. Marijne Heeren
Henry J. M. A. A. Zijlmans
Marij J. P. Welters
Joost H. van den Berg
Daisy Philips
Pia Kvistborg
Ilina Ehsan
Suzy M. E. Scholl
Bastiaan Nuijen
Ton N. M. Schumacher
Marc van Beurden
Ekaterina S. Jordanova
John B. A. G. Haanen
Sjoerd H. van der Burg
Gemma G. Kenter
Publikationsdatum: 27.04.2017
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 9/2017
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-017-2006-y

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HPV16 E7 DNA tattooing: safety, immunogenicity, and clinical response in patients with HPV-positive vulvar intraepithelial neoplasia