A gynecologic oncology group phase II trial of two p53 peptide vaccine approaches: subcutaneous injection and intravenous pulsed dendritic cells in high recurrence risk ovarian cancer patients.
A gynecologic oncology group phase II trial of two p53 peptide vaccine approaches: subcutaneous injection and intravenous pulsed dendritic cells in high recurrence risk ovarian cancer patients.
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DOI：
10.1007/s00262-011-1100-9
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发表时间：
2012-03
影响因子：
5.8
通讯作者：
Khleif, Samir N.
中科院分区：
文献类型：
--
作者：
Rahma, Osama E.;Ashtar, Ed;Czystowska, Malgorzata;Szajnik, Marta E.;Wieckowski, Eva;Bernstein, Sarah;Herrin, Vincent E.;Shams, Mortada A.;Steinberg, Seth M.;Merino, Maria;Gooding, William;Visus, Carmen;DeLeo, Albert B.;Wolf, Judith K.;Bell, Jeffrey G.;Berzofsky, Jay A.;Whiteside, Theresa L.;Khleif, Samir N.
肽抗原已经通过不同的方法作为癌症疫苗治疗来施用，包括直接注射或脉冲到树突状细胞上;然而，最佳递送方法仍有争议。在这项研究中，我们描述了两种疫苗的方法，使用野生型（WT）p53疫苗引起的免疫反应。21例HLA-A2.1患者，III期、IV期或复发性卵巢癌过表达p53蛋白，无疾病证据，分为两组接受治疗。A组接受与Montanide和GM-CSF混合的SC wt p53：264-272肽。臂B接受wt p53：264-272肽脉冲的树突状细胞IV。在交替周期中对两个队列给予白细胞介素-2（IL-2）。通过ELISPOT和四聚体测定，A组13名患者中的9名（69%）和B组6名患者中的5名（83%）出现免疫反应。疫苗没有引起严重的全身副作用。IL-2给药在两组中均导致3级和4级毒性，并直接诱导调节性T细胞的扩增。A组和B组的中位总生存期分别为40.8个月和29.6个月;中位无进展生存期分别为4.2个月和29.6个月。8.7月，分别。我们发现，使用任一种疫苗接种方法都能产生针对p53肽的相当的特异性免疫应答，且毒性最小。因此，我们的研究结果表明，使用要求较低的供应链方法可能是有效的。此外，使用低剂量SC IL-2作为佐剂可能会干扰免疫应答。因此，在未来的试验中可能不需要。
Peptide antigens have been administered by different approaches as cancer vaccine therapy, including direct injection or pulsed onto dendritic cells; however, the optimal delivery method is still debatable. In this study, we describe the immune response elicited by two vaccine approaches using the wild-type (wt) p53 vaccine. Twenty-one HLA-A2.1 patients with stage III, IV, or recurrent ovarian cancer over-expressing the p53 protein with no evidence of disease were treated in two cohorts. Arm A received SC wt p53:264-272 peptide admixed with Montanide and GM-CSF. Arm B received wt p53:264-272 peptide-pulsed dendritic cells IV. Interleukin-2 (IL-2) was administered to both cohorts in alternative cycles. Nine of 13 patients (69%) in arm A and 5 of 6 patients (83%) in arm B developed an immunologic response as determined by ELISPOT and tetramer assays. The vaccine caused no serious systemic side effects. IL-2 administration resulted in grade 3 and 4 toxicities in both arms and directly induced the expansion of T regulatory cells. The median overall survival was 40.8 and 29.6 months for arm A and B, respectively; the median progression-free survival was 4.2 and. 8.7 months, respectively. We found that using either vaccination approach generates comparable specific immune responses against the p53 peptide with minimal toxicity. Accordingly, our findings suggest that the use of less demanding SC approach may be as effective. Furthermore, the use of low-dose SC IL-2 as an adjuvant might have interfered with the immune response. Therefore, it may not be needed in future trials.
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影响因子：
82.9
作者：
Rosenberg, SA;Yang, JC;White, DE
通讯作者：
White, DE
影响因子：
11.5
作者：
Bergmann, Christoph;Strauss, Laura;Whiteside, Theresa L.
通讯作者：
Whiteside, Theresa L.
影响因子：
4.3
作者：
Gabrilovich, DI;Nadaf, S;Carbone, DP
通讯作者：
Carbone, DP
影响因子：
3.9
作者：
Khleif, SN;Abrams, SI;Schlom, J
通讯作者：
Schlom, J
影响因子：
5.2
作者：
Lemoine, Francois M.;Cherai, Mustapha;Lacave, Roger
通讯作者：
Lacave, Roger