PMID- 24824905
OWN - NLM
STAT- MEDLINE
DCOM- 20141222
LR  - 20221207
IS  - 1097-0215 (Electronic)
IS  - 0020-7136 (Linking)
VI  - 136
IP  - 1
DP  - 2015 Jan 1
TI  - Identification of promiscuous HPV16-derived T helper cell epitopes for 
      therapeutic HPV vaccine design.
PG  - 212-24
LID - 10.1002/ijc.28968 [doi]
AB  - Cervical carcinoma and several other human papillomavirus (HPV)-induced 
      malignancies are a global public health problem, thus novel treatment modalities 
      are urgently needed. Immunotherapy is an attractive option for treatment of HPV 
      infection and HPV-mediated premalignant and malignant lesions. However, previous 
      approaches--focusing on the induction of cytotoxic CD8+ T cells (CTLs)--have as 
      yet not yielded clinical successes. Since CD4+ T cells have been shown to be 
      crucial for the induction and maintenance of CTL responses, and more recently to 
      be also important for direct anti-tumor immunity, human leukocyte antigen (HLA) 
      class II-restricted epitopes are intensively investigated to improve the efficacy 
      of peptide-based HPV immunotherapy. We here present an approach to identify 
      promiscuous HPV16-derived CD4+ T helper epitopes, which are capable of inducing T 
      cell immunity in a large proportion of the population. To this end, we combined 
      HLA class II epitope prediction servers with in vitro immunological evaluation to 
      identify HPV16 E2-, E5-, E6-, and E7-derived CD4+ T cell epitopes. Candidate 
      selected HPV16-derived epitopes were found to be restricted by up to nine HLA-DR 
      molecules. Furthermore, they were found to induce frequent and robust HPV16 
      peptide-specific Th1 responses in healthy donors, as monitored by interferon 
      (IFN)-gamma ELISPOT and cytokine secretion assays. Moreover, these selected peptides 
      also induced specific IFN-gamma T cell responses in blood from HPV16+ CIN2/3 and 
      cervical carcinoma patients. We thus conclude that the identified T helper 
      epitopes are valuable candidates for the development of a comprehensive 
      therapeutic HPV vaccine.
CI  - (c) 2014 UICC.
FAU - Grabowska, Agnieszka K
AU  - Grabowska AK
AD  - Immunotherapy and -prevention, German Cancer Research Center (DKFZ), Heidelberg, 
      Germany.
FAU - Kaufmann, Andreas M
AU  - Kaufmann AM
FAU - Riemer, Angelika B
AU  - Riemer AB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140527
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (Cancer Vaccines)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Peptide Fragments)
RN  - 0 (Viral Proteins)
SB  - IM
MH  - Amino Acid Sequence
MH  - CD4-Positive T-Lymphocytes/immunology/virology
MH  - Cancer Vaccines/immunology
MH  - Cells, Cultured
MH  - Epitopes, T-Lymphocyte/*immunology
MH  - Female
MH  - Human papillomavirus 16/*immunology
MH  - Humans
MH  - Molecular Sequence Data
MH  - Papillomavirus Infections/immunology/*prevention & control/virology
MH  - Peptide Fragments/chemistry/immunology
MH  - Th1 Cells/*immunology/virology
MH  - Uterine Cervical Neoplasms/immunology/*prevention & control/virology
MH  - *Vaccination
MH  - Viral Proteins/chemistry/immunology
MH  - Uterine Cervical Dysplasia/immunology/*prevention & control/virology
OTO - NOTNLM
OT  - CD4+ T cell epitope
OT  - CD4+ T cell immunity
OT  - cervical cancer
OT  - human papillomavirus
OT  - tumor immunotherapy
EDAT- 2014/05/16 06:00
MHDA- 2014/12/23 06:00
CRDT- 2014/05/15 06:00
PHST- 2013/10/23 00:00 [received]
PHST- 2014/05/05 00:00 [accepted]
PHST- 2014/05/15 06:00 [entrez]
PHST- 2014/05/16 06:00 [pubmed]
PHST- 2014/12/23 06:00 [medline]
AID - 10.1002/ijc.28968 [doi]
PST - ppublish
SO  - Int J Cancer. 2015 Jan 1;136(1):212-24. doi: 10.1002/ijc.28968. Epub 2014 May 27.