Pre-immature dendritic cells PIDC pulsed with HPV16 E6 or E7 peptide are capable of eliciting specific immune response in patients with advanced cervical cancerReportar como inadecuado




Pre-immature dendritic cells PIDC pulsed with HPV16 E6 or E7 peptide are capable of eliciting specific immune response in patients with advanced cervical cancer - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Journal of Translational Medicine

, 12:353

First Online: 16 December 2014Received: 09 October 2014Accepted: 02 December 2014DOI: 10.1186-s12967-014-0353-4

Cite this article as: Rahma, O.E., Herrin, V.E., Ibrahim, R.A. et al. J Transl Med 2014 12: 353. doi:10.1186-s12967-014-0353-4

Abstract

BackgroundThe protein products of the early genes E6 and E7 in high-risk HPV types 16 and 18 have been implicated in the oncogenic capability of these viruses. Therefore, these peptides represent attractive vaccine therapy targets.

MethodsThirty-two patients with advanced cervical cancer HPV16 or 18 positive were treated with HPV16 E6 18–26 Arm A or HPV16 E7 12–20 peptide Arm B pulsed on PBMCs in order to illicit immune response against the relevant peptide on both arms. These PBMCs were cultured for a short time 48 hours only and in the presence of GM- CSF, accordingly, they were identified as -Pre-Immature Dentritic Cells-.

Results51Cr release assay and ELISPOT demonstrated evidence of specific immune response against the relevant peptide in 10-16 63% evaluable patients in arm A and 7-12 58% in arm B. HPV16 E6 was found to be homologous to HPV18 E6 in both vivo and vitro. The median overall survival OS and progression free survival PFS for the full cohort was 10.0 and 3.5 months, respectively. There were no RECIST responses in any patient. The majority of toxicities were grade I and II.

ConclusionsWe demonstrated the feasibility and ability of Pre-Immature Dentritic Cells pulsed with HPV16 E6 18–26 or HPV16 E7 12–20 to induce a specific immune response against the relevant peptide despite the advanced disease of the cervical cancer patients treated on this trial. We believe that this observation deserves further investigations.

KeywordsDendritic cells HPV16 E6 E7 Vaccine Cervical cancer AbbreviationsPIDCPre-immature dendritic cells

HPVHuman papilloma virus

PBMCsPeripheral blood mononuclear cell

GM- CSFGranulocyte macrophage colony-stimulating factor

51Cr releaseChromium-51 release assay

ELISPOTEnzyme-linked ImmunoSpot

OSOverall survival

PFSProgression free survival

RECISTResponse evaluation criteria

DCsDendritic cells

ILInterleukin

ECOGEastern cooperative oncology group

NCINational cancer institute

NNMCNational naval medical center

IRBsInstitutional review boards

MNCsPeripheral blood mononuclear cells

AphAutomated leukapheresis

WBWhole blood

IVIntravenously IV

CTLCytotoxic T Lymphocyte

TLNTumor-draining lymph nodes

APC’sAntigen presenting cells

IFN-gammaInterferon-gamma

Electronic supplementary materialThe online version of this article doi:10.1186-s12967-014-0353-4 contains supplementary material, which is available to authorized users.

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Autor: Osama E Rahma - Vincent E Herrin - Rami A Ibrahim - Anton Toubaji - Sarah Bernstein - Omar Dakheel - Seth M Steinberg -

Fuente: https://link.springer.com/







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