Immunization with human papillomavirus type 16 (HPV16) oncoprotein-loaded dendritic cells as well as protein in adjuvant induces MHC class I-restricted protection to HPV16-induced tumor cells

Human papillomavirus (HPV) E6 and E7 oncoproteins are attractive targets for T-cell-based immunotherapy of cervical cancer. In this study, we demonstrate that dendritic cells (DCs) pulsed with HPV16 E7 protein are not only recognized in vitro by E7-specific CTLs but also elicit E7-specific CTL respo...

Full description

Saved in:
Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1998-02, Vol.58 (4), p.724-731
Main Authors: DE BRUIJN, M. L. H, SCHUURHUIS, D. H, OTTENHOFF, T. H. M, OFFRINGA, R, MELIEF, C. J. M, VIERBOOM, M. P. M, VERMEULEN, H, DE COCK, K. A. J, OOMS, M. E, RESSING, M. E, TOEBES, M, FRANKEN, K. L. M. C, DRIJFHOUT, J.-W
Format: Article
Language:English
Subjects:
AIDS/HIV
Animals
Antineoplastic agents
Biological and medical sciences
Cancer Vaccines - immunology
CD4-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - immunology
Cytotoxicity, Immunologic
Dendritic Cells - immunology
Freund's Adjuvant - immunology
Histocompatibility Antigens Class I - immunology
Immunotherapy
Medical sciences
Mice
Mice, Inbred BALB C
Oncogene Proteins, Viral - immunology
Papillomaviridae - pathogenicity
Papillomavirus E7 Proteins
Pharmacology. Drug treatments
Tumor Virus Infections - prevention & control
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Human papillomavirus (HPV) E6 and E7 oncoproteins are attractive targets for T-cell-based immunotherapy of cervical cancer. In this study, we demonstrate that dendritic cells (DCs) pulsed with HPV16 E7 protein are not only recognized in vitro by E7-specific CTLs but also elicit E7-specific CTL responses in vivo, associated with protection against a challenge with syngeneic HPV16-induced tumor cells. Vaccination with soluble E7 protein in incomplete Freund's adjuvant likewise induces E7-specific CTL responses associated with tumor protection. The presence of HPV16 E7-specific CTLs in vivo and the observation that depletion of CD8+ cells completely abolishes tumor protection demonstrate that CTLs are the major effector cells in mediating antitumor activity. The in vivo involvement of DCs in the activation of protective CTLs is suggested by the surface display of E7 peptide-loaded MHC class I molecules on these cells after E7 protein immunization. These data show that HPV16 E7 protein-pulsed DCs, as well as the administration of E7 protein antigen in adjuvant, can effectively stimulate tumor-specific MHC class I-restricted CD8+ T-cell-mediated protective immunity to HPV16-induced cancers.
ISSN:0008-5472
1538-7445