Vaccination of colorectal cancer patients with TroVax given alongside chemotherapy (5-fluorouracil, leukovorin and irinotecan) is safe and induces potent immune responses
Vaccination of colorectal cancer patients with TroVax given alongside chemotherapy (5-fluorouracil, leukovorin and irinotecan) is safe and induces potent immune responses
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DOI：
10.1007/s00262-007-0428-7
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发表时间：
2008-07-01
影响因子：
5.8
通讯作者：
Hawkins, Robert E.
中科院分区：
文献类型：
--
作者：
Harrop, Richard;Drury, Noel;Hawkins, Robert E.
编码肿瘤抗原5T4的修饰安卡拉牛痘（MVA） （TroVax((R))）已经在转移性结直肠癌患者的开放标签II期研究中进行了评估。主要目的是评估在5-氟尿嘧啶、白vorin和伊立替康治疗之前、期间和之后注射TroVax的安全性和免疫原性。对19例转移性结直肠癌患者给予TroVax治疗。6次注射后抽取了12例患者的血液样本，这些样本被认为可用于评估免疫反应。在整个研究过程中监测肿瘤抗原5T4和病毒载体MVA特异性的抗体和细胞反应。在化疗的同时使用TroVax是安全且耐受性良好的，没有由于疫苗引起的SAEs，也没有化学相关毒性的增强。在12例可评估免疫反应的患者中，10例携带5t4特异性抗体反应，滴度从10到50 000不等。在11例患者中检测到特异性针对5T4的IFN γ ELISPOT反应，其中5例患者的频率超过千分之一。8例患者出现循环CEA浓度升高，其中6例在化疗期间下降超过50%，4例CEA水平在化疗结束后1个月内保持稳定。在19例意向治疗（ITT）患者中，1例有CR， 6例有pr， 5例有SD。在所有12例可评估的患者中诱导了有效的5t4特异性细胞和/或体液免疫反应，并且在给予化疗期间在大多数患者中可检测到。这些数据表明，TroVax可以在化疗方案之上分层，没有任何证据表明毒性增强或免疫或治疗效果降低。
Modified vaccinia Ankara (MVA) encoding the tumor antigen 5T4 (TroVax((R))) has been evaluated in an open label phase II study in metastatic colorectal cancer patients. The primary objective was to assess the safety and immunogenicity of TroVax injected before, during and after treatment with 5-fluorouracil, leukovorin and irinotecan. TroVax was administered to 19 patients with metastatic colorectal cancer. Twelve patients had blood samples taken following each of the six injections and were considered to be evaluable for assessment of immunological responses. Both antibody and cellular responses specific for the tumor antigen 5T4 and the viral vector MVA were monitored throughout the study. Administration of TroVax alongside chemotherapy was safe and well tolerated with no SAEs attributed to the vaccine and no enhancement of chemo-related toxicity. Of the 12 patients who were evaluable for assessment of immune responses, ten mounted 5T4-specific antibody responses with titers ranging from 10 to > 5,000. IFN gamma ELISPOT responses specific for 5T4 were detected in 11 patients with frequencies exceeding one in 1,000 PBMCs in five patients. Eight patients presented with elevated circulating CEA concentrations, six of whom showed decreases in excess of 50% during chemotherapy and four had CEA levels which remained stable for > 1 month following completion of chemotherapy. Of the 19 intention to treat (ITT) patients, one had a CR, six had PRs and five had SD. Potent 5T4-specific cellular and/or humoral immune responses were induced in all 12 evaluable patients and were detectable in most patients during the period in which chemotherapy was administered. These data demonstrate that TroVax can be layered on top of chemotherapy regimens without any evidence of enhanced toxicity or reduced immunological or therapeutic efficacy.