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

Journal of Translational Medicine

Samir N Khleif⁴  Jay A Berzofsky¹  Mikayel Mkrtichyan⁴  Rasha Abu Eid⁴  Seth M Steinberg²  Omar Dakheel¹  Sarah Bernstein³  Anton Toubaji¹  Rami A Ibrahim¹  Vincent E Herrin¹  Osama E Rahma⁵ 

[1] Cancer Vaccine Branch, CCR, NCI, 10 Center Drive, Bethesda 20892, MD, USA;Biostatistics and Data Management Section, CCR, NCI, 9609 Medical Center Drive, Rockville 20850, MD, USA;Walter Reed National Military Medical Center, 8901 Wisconsin Ave, Bethesda 20814, MD, USA;Georgia Regents University Cancer Center, 1411 Laney Walker Blvd, Augusta 30912, GA, USA;University of Virginia, Charlottesville 22908, VA, USA

关键词: Cervical cancer;    Vaccine;    E7;    E6;    HPV16;    Dendritic cells;   

Others  :  1146578
DOI  :  10.1186/s12967-014-0353-4

 received in 2014-10-09, accepted in 2014-12-02,  发布年份 2014

【 摘 要 】

Background

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. Therefore, these peptides represent attractive vaccine therapy targets.

Methods

Thirty-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”.

Results

51Cr 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.

Conclusions

We 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.

【 授权许可】

   
2014 Rahma et al.; licensee BioMed Central Ltd.

【 图 表 】

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