Del Vecchio Catherine A, Wong Albert J
Stanford University, 300 Pasteur Drive, Edwards R213, Stanford, CA 94305, USA.
Curr Opin Mol Ther. 2010 Dec;12(6):741-54.
Celldex Therapeutics is developing rindopepimut (CDX-110), a 14-mer injectable peptide vaccine for the potential treatment of glioblastoma multiforme (GBM). Rindopepimut specifically targets a novel junctional epitope of the EGFR deletion mutant EGFRvIII, which is a constitutively active receptor that is expressed in approximately 60 to 70% of patients with GBM. EGFRvIII expression is correlated with worse prognosis and reduced overall survival. Importantly, EGFRvIII is not expressed in normal brain tissue, making it an excellent therapeutic target. Preclinical studies demonstrated lasting tumor regression and increased survival times, as well as efficient generation of EGFRvIII-specific humoral and cellular immune responses, in animals expressing EGFRvIII and vaccinated with rindopepimut. Phase I and II clinical trials in patients with GBM demonstrated significantly increased median time to progression and overall survival time in those vaccinated with rindopepimut compared with matched historical controls. Only limited side effects have been observed in patients. Given these results, rindopepimut is an extremely promising therapy for patients with GBM. Phase I and II clinical trials in patients with GBM were ongoing at the time of publication. In the future, it may be beneficial to combine rindopepimut with other treatment modalities to further prolong survival.
赛尔迪克斯治疗公司正在研发rindopepimut（CDX - 110），这是一种由14个氨基酸组成的注射用肽疫苗，用于潜在治疗多形性胶质母细胞瘤（GBM）。Rindopepimut特异性靶向表皮生长因子受体（EGFR）缺失突变体EGFRvIII的一个新的连接表位，EGFRvIII是一种组成型激活受体，在约60%至70%的GBM患者中表达。EGFRvIII的表达与较差的预后和缩短的总生存期相关。重要的是，EGFRvIII在正常脑组织中不表达，使其成为一个理想的治疗靶点。临床前研究表明，在表达EGFRvIII并接种rindopepimut的动物中，可出现持久的肿瘤消退和生存期延长，以及高效产生EGFRvIII特异性体液和细胞免疫反应。针对GBM患者的I期和II期临床试验表明，与匹配的历史对照相比，接种rindopepimut的患者的中位进展时间和总生存期显著延长。在患者中仅观察到有限的副作用。鉴于这些结果，rindopepimut对GBM患者来说是一种极有前景的治疗方法。在发表本文时，针对GBM患者的I期和II期临床试验正在进行。未来，将rindopepimut与其他治疗方式联合使用可能有助于进一步延长生存期。
