Rahma Osama E, Herrin Vincent E, Ibrahim Rami A, Toubaji Anton, Bernstein Sarah, Dakheel Omar, Steinberg Seth M, Abu Eid Rasha, Mkrtichyan Mikayel, Berzofsky Jay A, Khleif Samir N
Cancer Vaccine Branch, CCR, NCI, 10 Center Drive, Bethesda 20892, MD, USA.
J Transl Med. 2014 Dec 16;12:353. doi: 10.1186/s12967-014-0353-4.
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.
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".
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.
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.
高危型人乳头瘤病毒16型和18型的早期基因E6和E7的蛋白产物与这些病毒的致癌能力有关。因此，这些肽代表了有吸引力的疫苗治疗靶点。
32例晚期宫颈癌患者（HPV16或18阳性）接受HPV16 E6（18 - 26）（A组）或HPV16 E7（12 - 20）肽（B组）脉冲处理的外周血单核细胞治疗，以引发双臂针对相关肽的免疫反应。这些外周血单核细胞仅短期培养（48小时）并在GM - CSF存在的情况下培养，因此被鉴定为“前未成熟树突状细胞”。
51Cr释放试验和ELISPOT证明，A组16例可评估患者中有10例（63%）、B组12例中有7例（58%）出现针对相关肽的特异性免疫反应证据。发现HPV16 E6在体内和体外均与HPV18 E6同源。整个队列的中位总生存期（OS）和无进展生存期（PFS）分别为10.0个月和3.5个月。所有患者均无RECIST反应。大多数毒性为I级和II级。
我们证明了用HPV16 E6（18 - 26）或HPV16 E7（12 - 20）脉冲处理的前未成熟树突状细胞诱导针对相关肽的特异性免疫反应的可行性和能力，尽管本试验中治疗的宫颈癌患者病情已进展。我们认为这一观察结果值得进一步研究。
