DNA fusion-gene vaccination in patients with prostate cancer induces high-frequency CD8(+) T-cell responses and increases PSA doubling time.
DNA fusion-gene vaccination in patients with prostate cancer induces high-frequency CD8(+) T-cell responses and increases PSA doubling time.
复制标题
DOI：
10.1007/s00262-012-1270-0
复制
发表时间：
2012-11
影响因子：
5.8
通讯作者：
Ottensmeier, Christian
中科院分区：
文献类型：
--
作者：
Chudley, Lindsey;McCann, Katy;Mander, Ann;Tjelle, Torunn;Campos-Perez, Juan;Godeseth, Rosemary;Creak, Antonia;Dobbyn, James;Johnson, Bernadette;Bass, Paul;Heath, Catherine;Kerr, Paul;Mathiesen, Iacob;Dearnaley, David;Stevenson, Freda;Ottensmeier, Christian
我们报告的免疫原性和临床效果的I/II期剂量递增试验的DNA融合疫苗在前列腺癌患者。该疫苗编码来自破伤风毒素片段C的结构域（DOM），该结构域连接至来自前列腺特异性膜抗原（PSMA）的HLA-A2结合表位，PSMA 27 -35。我们评估了肌肉内接种（无或有电穿孔（EP））对疫苗效力的影响。32名HLA-A2+患者接受了疫苗接种，并在72周的随访期内监测免疫和临床反应。在第24周，允许交叉到免疫学上更有效的给药方式;这是基于早期抗体数据的EP，随后，13/15例患者交叉到+EP组。32例HLA-A2-对照患者评估了下一次治疗的时间和总生存期。疫苗接种是安全的，耐受性良好。疫苗诱导DOM特异性CD 4+和PSMA 27特异性CD 8 + T细胞，其在研究结束时以高于基线的显著水平可检测到（分别为p = 0.0223和p = 0.00248）。在30名患者中，29名具有可测量的CD 4 + T细胞应答，并且在16/30名患者中检测到PSMA 27特异性CD 8 + T细胞，有或没有EP。在第24周，在交叉之前，两种递送方法均导致增加的CD 4+和CD 8+疫苗特异性T细胞，其中EP具有更大效果的趋势。PSA倍增时间从治疗前的11.97个月显著增加至72周随访期间的16.82个月（p = 0.0417），EP无明显差异效应。对DOM-PSMA 27疫苗接种的免疫应答的高频率和临床效果是足够有希望的，以保证进一步的随机测试。本文的在线版本（doi：10.1007/s 00262 -012-1270-0）包含补充材料，可供授权用户使用。
We report on the immunogenicity and clinical effects in a phase I/II dose escalation trial of a DNA fusion vaccine in patients with prostate cancer. The vaccine encodes a domain (DOM) from fragment C of tetanus toxin linked to an HLA-A2-binding epitope from prostate-specific membrane antigen (PSMA), PSMA27–35. We evaluated the effect of intramuscular vaccination without or with electroporation (EP) on vaccine potency. Thirty-two HLA-A2+ patients were vaccinated and monitored for immune and clinical responses for a follow-up period of 72 weeks. At week 24, cross-over to the immunologically more effective delivery modality was permitted; this was shown to be with EP based on early antibody data, and subsequently, 13/15 patients crossed to the +EP arm. Thirty-two HLA-A2− control patients were assessed for time to next treatment and overall survival. Vaccination was safe and well tolerated. The vaccine induced DOM-specific CD4+ and PSMA27-specific CD8+ T cells, which were detectable at significant levels above baseline at the end of the study (p = 0.0223 and p = 0.00248, respectively). Of 30 patients, 29 had a measurable CD4+ T-cell response and PSMA27-specific CD8+ T cells were detected in 16/30 patients, with or without EP. At week 24, before cross-over, both delivery methods led to increased CD4+ and CD8+ vaccine-specific T cells with a trend to a greater effect with EP. PSA doubling time increased significantly from 11.97 months pre-treatment to 16.82 months over the 72-week follow-up (p = 0.0417), with no clear differential effect of EP. The high frequency of immunological responses to DOM-PSMA27 vaccination and the clinical effects are sufficiently promising to warrant further, randomized testing. The online version of this article (doi:10.1007/s00262-012-1270-0) contains supplementary material, which is available to authorized users.
登录
查看更多内容
DOI：
10.1056/nejmoa1003466
发表时间：
2010-08-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hodi FS;O'Day SJ;McDermott DF;Weber RW;Sosman JA;Haanen JB;Gonzalez R;Robert C;Schadendorf D;Hassel JC;Akerley W;van den Eertwegh AJ;Lutzky J;Lorigan P;Vaubel JM;Linette GP;Hogg D;Ottensmeier CH;Lebbé C;Peschel C;Quirt I;Clark JI;Wolchok JD;Weber JS;Tian J;Yellin MJ;Nichol GM;Hoos A;Urba WJ
通讯作者：
Urba WJ
影响因子：
4.4
作者：
Ahlen, Gustaf;Soderholm, Jonas;Sallberg, Matti
通讯作者：
Sallberg, Matti
影响因子：
158.5
作者：
Kantoff, Philip W.;Higano, Celestia S.;Young, J.
通讯作者：
Young, J.
影响因子：
--
作者：
Perambakam S;Xie H;Edassery S;Peace DJ
通讯作者：
Peace DJ
影响因子：
6.6
作者：
North, S. A.;Graham, K.;Venner, P.
通讯作者：
Venner, P.