Phase 1 studies of the safety and immunogenicity of electroporated HER2/CEA DNA vaccine followed by adenoviral boost immunization in patients with solid tumors.
Phase 1 studies of the safety and immunogenicity of electroporated HER2/CEA DNA vaccine followed by adenoviral boost immunization in patients with solid tumors.
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DOI：
10.1186/1479-5876-11-62
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发表时间：
2013-03-08
影响因子：
7.4
通讯作者：
Montero AJ
中科院分区：
文献类型：
--
作者：
Diaz CM;Chiappori A;Aurisicchio L;Bagchi A;Clark J;Dubey S;Fridman A;Fabregas JC;Marshall J;Scarselli E;La Monica N;Ciliberto G;Montero AJ
DNA电穿孔已在临床前模型中被证明是一种有前途的改善癌症免疫力的策略，特别是当在异源初免-加强方案中与其他基因疫苗组合时。我们报告了2项多中心I期试验的结果，这些试验涉及II-IV期成人癌症患者（n=33）。患者接种单独的V930、含有等量的表达人HER 2的细胞外和跨膜结构域的质粒的DNA疫苗和表达与大肠杆菌不耐热毒素的B亚基融合的CEA的质粒（研究1），或用V930接着V932的异源初免-加强疫苗接种方法，编码相同抗原的双顺反子腺病毒亚型-6病毒载体疫苗（研究2）。单独使用V930疫苗接种与电穿孔或与V932联合使用耐受性良好，没有任何严重不良事件。在这两项研究中，最常见的疫苗相关副作用是注射部位反应和关节痛。通过ELISPOT在患者中未检测到对CEA或HER 2的可测量的细胞介导的免疫应答（CMI）;然而，在接种疫苗后观察到细胞介导的免疫力和针对细菌热不稳定毒素的抗体滴度均显著增加。V930疫苗接种单独或与V932组合耐受良好，没有任何疫苗相关的严重不良反应，并且能够诱导针对细菌抗原的可测量的免疫应答。然而，初免-加强策略似乎并没有增强任何针对CEA或HER 2的可检测到的CMI反应。研究1 -ClinicalTrials.gov，NCT 00250419;研究2 - ClinicalTrials.gov，NCT 00647114。
DNA electroporation has been demonstrated in preclinical models to be a promising strategy to improve cancer immunity, especially when combined with other genetic vaccines in heterologous prime-boost protocols. We report the results of 2 multicenter phase 1 trials involving adult cancer patients (n=33) with stage II-IV disease. Patients were vaccinated with V930 alone, a DNA vaccine containing equal amounts of plasmids expressing the extracellular and trans-membrane domains of human HER2, and a plasmid expressing CEA fused to the B subunit of Escherichia coli heat labile toxin (Study 1), or a heterologous prime-boost vaccination approach with V930 followed by V932, a dicistronic adenovirus subtype-6 viral vector vaccine coding for the same antigens (Study 2). The use of the V930 vaccination with electroporation alone or in combination with V932 was well-tolerated without any serious adverse events. In both studies, the most common vaccine-related side effects were injection site reactions and arthralgias. No measurable cell-mediated immune response (CMI) to CEA or HER2 was detected in patients by ELISPOT; however, a significant increase of both cell-mediated immunity and antibody titer against the bacterial heat labile toxin were observed upon vaccination. V930 vaccination alone or in combination with V932 was well tolerated without any vaccine-related serious adverse effects, and was able to induce measurable immune responses against bacterial antigen. However, the prime-boost strategy did not appear to augment any detectable CMI responses against either CEA or HER2. Study 1 – ClinicalTrials.gov, NCT00250419; Study 2 – ClinicalTrials.gov, NCT00647114.
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影响因子：
11.5
作者：
Aurisicchio, Luigi;Peruzzi, Daniela;La Monica, Nicola
通讯作者：
La Monica, Nicola
影响因子：
5.4
作者：
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影响因子：
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作者：
Kantoff, Philip W.;Higano, Celestia S.;Young, J.
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Young, J.
影响因子：
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作者：
Cipriani, Barbara;Fridman, Arthur;Scarselli, Elisa
通讯作者：
Scarselli, Elisa
影响因子：
2.2
作者：
Mander AP;Thompson SG
通讯作者：
Thompson SG