PMID- 11291058
OWN - NLM
STAT- MEDLINE
DCOM- 20010426
LR  - 20221207
IS  - 0020-7136 (Print)
IS  - 0020-7136 (Linking)
VI  - 92
IP  - 2
DP  - 2001 Apr 15
TI  - HPV16 L1E7 chimeric virus-like particles induce specific HLA-restricted T cells 
      in humans after in vitro vaccination.
PG  - 285-93
AB  - Cervical cancer has been shown to be highly associated with human papillomavirus 
      (HPV) infection. The viral oncogenes E6 and E7 are constantly expressed by the 
      tumor cells and are therefore targets for immunotherapy. In the present study we 
      investigated the potential of HPV16 L1E7 chimeric virus-like particles (CVLP) to 
      activate specific cytotoxic T lymphocytes in human blood donors. CVLP were 
      expressed by recombinant baculovirus and purified. Direct incubation of freshly 
      isolated peripheral blood lymphocytes (PBL) with CVLP resulted in induction of 
      proliferation and growth of T cell lines. To enhance antigen presentation we also 
      loaded dendritic cells with CVLP and used them to activate naive T cells. Growing 
      cell lines were mainly CD3 positive (>95%) with a predominant CD4-positive and a 
      minor CD8-positive component. Analysis of Tcell specificity was carried out by an 
      interferon-gamma ELISpot assay. Dendritic cells pseudoinfected with CVLP or 
      pulsed with human leukocyte antigen (HLA)-A*0201-restricted peptide E7(11-20) or 
      with a newly identified HPV16 peptide L1(323-331) were used as stimulator cells. 
      T cells responsive to CVLP were found in the cultures with frequencies of 
      0.5%-0.7%. Frequencies to peptides were around 0.1%. These T cells had cytolytic 
      activity toward autologous B-lymphoblastic cell lines either pseudoinfected with 
      CVLP or pulsed with HLA-A*0201-restricted peptides. They also lysed the HPV16- 
      and HLA-A*0201-positive cervical cancer cell line CaSki, whereas 
      HLA-A*0201-negative SiHa cells were not lysed. We conclude from our data that 
      CVLP show promise for a therapeutic vaccine in patients with HPV16-positive 
      cervical intraepithelial neoplasia lesions or cervical cancer.
CI  - Copyright 2001 Wiley-Liss, Inc.
FAU - Kaufmann, A M
AU  - Kaufmann AM
AD  - Gynecologic Molecular Biology, Department for Obstetrics and Gynecology, 
      Friedrich-Schiller-University Jena, Bachstrasse 18, 07740 Jena, Germany. 
      a.kaufmann@med.uni-jena.de
FAU - Nieland, J
AU  - Nieland J
FAU - Schinz, M
AU  - Schinz M
FAU - Nonn, M
AU  - Nonn M
FAU - Gabelsberger, J
AU  - Gabelsberger J
FAU - Meissner, H
AU  - Meissner H
FAU - Muller, R T
AU  - Muller RT
FAU - Jochmus, I
AU  - Jochmus I
FAU - Gissmann, L
AU  - Gissmann L
FAU - Schneider, A
AU  - Schneider A
FAU - Durst, M
AU  - Durst M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (Antigens, Viral)
RN  - 0 (Cancer Vaccines)
RN  - 0 (Capsid Proteins)
RN  - 0 (HLA-A Antigens)
RN  - 0 (HPV16 L1E7 chimeric virus-like particle)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (Oncogene Proteins, Viral)
RN  - 0 (Papillomavirus E7 Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (oncogene protein E7, Human papillomavirus type 16)
RN  - 6LTE2DNX63 (L1 protein, Human papillomavirus type 16)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Antigens, Viral/genetics/immunology
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - Cancer Vaccines/*therapeutic use
MH  - *Capsid Proteins
MH  - Cell Line
MH  - Cells, Cultured
MH  - Cytotoxicity Tests, Immunologic
MH  - Dendritic Cells/immunology
MH  - Female
MH  - HLA-A Antigens/immunology
MH  - Humans
MH  - Interferon-gamma/biosynthesis
MH  - Lymphocyte Activation
MH  - Oncogene Proteins, Fusion/genetics/*immunology
MH  - Oncogene Proteins, Viral/genetics/*immunology
MH  - Papillomavirus E7 Proteins
MH  - Recombinant Fusion Proteins/genetics/immunology
MH  - T-Lymphocyte Subsets/immunology
MH  - T-Lymphocytes, Cytotoxic/*immunology
MH  - Uterine Cervical Neoplasms/immunology/*therapy/virology
MH  - Virion/genetics/immunology
MH  - Uterine Cervical Dysplasia/immunology/*therapy/virology
EDAT- 2001/04/06 10:00
MHDA- 2001/05/01 10:01
CRDT- 2001/04/06 10:00
PHST- 2001/04/06 10:00 [pubmed]
PHST- 2001/05/01 10:01 [medline]
PHST- 2001/04/06 10:00 [entrez]
AID - 10.1002/1097-0215(200102)9999:9999<::AID-IJC1181>3.0.CO;2-Q [pii]
AID - 10.1002/1097-0215(200102)9999:9999<::aid-ijc1181>3.0.co;2-q [doi]
PST - ppublish
SO  - Int J Cancer. 2001 Apr 15;92(2):285-93. doi: 
      10.1002/1097-0215(200102)9999:9999<::aid-ijc1181>3.0.co;2-q.