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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-014-0353-4) contains supplementary material, which is available to authorized users.
Highlights
The protein products of the early genes E6 and E7 in high-risk human papillomavirus (HPV) types 16 and 18 have been implicated in the oncogenic capability of these viruses
are summarized in Table 1 (Arm A) received HPV16 E6 (18–26) peptide, while patients on arm B received HPV16 E7 (12–20) peptide pulsed on preimmature dendritic cells (PIDCs)
Path Pathology (Patient) who received the E6 peptide harbored either HPV16 or 18 in their tumors, whereas patients who received the E7 peptide harbored HPV16 (Tables 1 and 2). These selection criteria were based on our pre-clinical studies which showed that HPV16 E6 (18–26) and HPV18 E6 (13–21) peptides are homologous
Summary
The 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. These peptides represent attractive vaccine therapy targets. High-risk human papillomavirus (HPV) has been implicated as an etiologic factor in almost all cervical cancers [2]. The recent development and FDA approval of two vaccines for HPV infection have represented a major advance in cervical cancer prevention [5,6,7,8]. Better therapeutic modalities for advanced cervical cancer are needed
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