Phase I trial of sequential administration of recombinant DNA and adenovirus expressing L523S protein in early stage non-small-cell lung cancer
Phase I trial of sequential administration of recombinant DNA and adenovirus expressing L523S protein in early stage non-small-cell lung cancer
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DOI：
10.1016/j.ymthe.2006.01.013
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发表时间：
2006-06-01
影响因子：
12.4
通讯作者：
Cheever, MA
中科院分区：
文献类型：
--
作者：
Nemunaitis, J;Meyers, T;Cheever, MA
L523S是一种免疫原性肺癌抗原，当该基因以表达质粒(pVAX/L5235)的形式肌肉注射，并与EL B缺失腺病毒(Ad/L523S)整合后传递时，已显示出临床前的安全性。我们对13例IB、IIA和IIB期非小细胞肺癌患者进行了I期临床试验。PVAX/L523S(第0、14天各8 mg)和Ad/L523S(第1、20、400×10(9)VP，第28、56天，第1、2、3组各3例)。未发现明显的毒性作用。除1例患者外，其余患者抗腺病毒抗体均升高两倍以上。10例可评价患者中有1例直接免疫球蛋白夹心法检测到L523S特异性抗体。两名患者出现疾病复发，在中位数290天的随访后全部存活。结果表明，L523S具有很高的安全性，但L523S直接免疫激活的证据有限，这表明需要修改疫苗的剂量、时间表和接种地点(即皮内接种)，并进行进一步的临床试验。
L523S is an immunogenic lung cancer antigen that has demonstrated preclinical safety when the gene is injected intramuscularly as an expressive plasmid (pVAX/L5235) and when delivered following incorporation into an El B-deleted adenovirus (Ad/L523S). We performed a phase I clinical trial in 13 stage IB, IIA, and IIB non-small-cell lung cancer patients. pVAX/L523S (8 mg on days 0 and 14 in all cohorts) and Ad/L523S (1, 20, 400 x 10(9) vp on days 28 and 56, cohorts 1, 2, and 3, respectively) were administered to 3 patients in each of three cohorts. No significant toxic effect was identified. All but 1 patient demonstrated greater than or equal to twofold elevation in anti-adenovirus antibodies. One of 10 evaluable patients demonstrated L523S-specific antibody by direct IgG ELISA. Two patients developed disease recurrence and all remain alive after a median of 290 days follow-up. Results suggest a high level of safety but evidence of L523S-directed immune activation was limited, suggesting a need for modification of dose, schedule, and site of vaccination (i.e., intradermal) with further clinical testing.