Imperial College London
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ProfessorNagyHabib

Faculty of Medicine, Department of Surgery & Cancer

Professor of Hepatobiliary Surgery
 
 
 
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Contact

 

+44 (0)20 3313 8574nagy.habib

 
 
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Assistant

 

Mrs Benita White +44 (0)7960 986 387

 
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Location

 

BN1/18 B BlockHammersmith HospitalHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Aloysius:2009:10.1186/1479-5876-7-18,
author = {Aloysius, MM and Mc, Kechnie AJ and Robins, RA and Verma, C and Eremin, JM and Farzaneh, F and Habib, NA and Bhalla, J and Hardwick, NR and Satthaporn, S and Sreenivasan, T and El-Sheemy, M and Eremin, O},
doi = {10.1186/1479-5876-7-18},
journal = {Journal of Translational Medicine},
title = {Generation in vivo of peptide-specific cytotoxic T cells and presence of regulatory T cells during vaccination with hTERT (class I and II) peptide-pulsed DCs},
url = {http://dx.doi.org/10.1186/1479-5876-7-18},
volume = {7},
year = {2009}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BackgroundOptimal techniques for DC generation for immunotherapy in cancer are yet to be established. Study aims were to evaluate: (i) DC activation/maturation milieu (TNF-α +/- IFN-α) and its effects on CD8+ hTERT-specific T cell responses to class I epitopes (p540 or p865), (ii) CD8+ hTERT-specific T cell responses elicited by vaccination with class I alone or both class I and II epitope (p766 and p672)-pulsed DCs, prepared without IFN-α, (iii) association between circulating T regulatory cells (Tregs) and clinical responses.MethodsAutologous DCs were generated from 10 patients (HLA-0201) with advanced cancer by culturing CD14+ blood monocytes in the presence of GM-CSF and IL-4 supplemented with TNF-α [DCT] or TNF-α and IFN-α [DCTI]. The capacity of the DCs to induce functional CD8+ T cell responses to hTERT HLA-0201 restricted nonapeptides was assessed by MHC tetramer binding and peptide-specific cytotoxicity. Each DC preparation (DCT or DCTI) was pulsed with only one type of hTERT peptide (p540 or p865) and both preparations were injected into separate lymph node draining regions every 2–3 weeks. This vaccination design enabled comparison of efficacy between DCT and DCTI in generating hTERT peptide specific CD8+ T cells and comparison of class I hTERT peptide (p540 or p865)-loaded DCT with or without class II cognate help (p766 and p672) in 6 patients. T regulatory cells were evaluated in 8 patients.Results(i) DCTIs and DCTs, pulsed with hTERT peptides, were comparable (p = 0.45, t-test) in inducing peptide-specific CD8+ T cell responses. (ii) Class II cognate help, significantly enhanced (p < 0.05, t-test) peptide-specific CD8+T cell responses, compared with class I pulsed DCs alone. (iii) Clinical responders had significantly lower (p < 0.05, Mann-Whitney U test) T regs, compared with non-responders. 4/16 patients experienced partial but transient clinical responses during vaccination. Vaccination was well tolera
AU  - Aloysius,MM
AU  - Mc,Kechnie AJ
AU  - Robins,RA
AU  - Verma,C
AU  - Eremin,JM
AU  - Farzaneh,F
AU  - Habib,NA
AU  - Bhalla,J
AU  - Hardwick,NR
AU  - Satthaporn,S
AU  - Sreenivasan,T
AU  - El-Sheemy,M
AU  - Eremin,O
DO  - 10.1186/1479-5876-7-18
PY  - 2009///
SN  - 1479-5876
TI  - Generation in vivo of peptide-specific cytotoxic T cells and presence of regulatory T cells during vaccination with hTERT (class I and II) peptide-pulsed DCs
T2  - Journal of Translational Medicine
UR  - http://dx.doi.org/10.1186/1479-5876-7-18
UR  - http://hdl.handle.net/10044/1/38660
VL  - 7
ER  -
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