肿瘤异质性作为自体肾细胞癌肿瘤疫苗中多表位方法的理论依据。
Tumor heterogeneity as a rationale for a multi-epitope approach in an autologous renal cell cancer tumor vaccine.
作者信息
Wittke Stefan, Baxmann Susann, Fahlenkamp Dirk, Kiessig Stephan T
机构信息
University of Applied Sciences Bremerhaven, Faculty of Biotechnology Bremerhaven, Bochum, Germany.
Ruhr-Plasma-Centre GmbH, Bochum, Germany.
出版信息
Onco Targets Ther. 2016 Jan 27;9:523-37. doi: 10.2147/OTT.S92182. eCollection 2016.
PURPOSE
An autologous tumor vaccine already used successfully in the immune therapy of renal cell carcinoma was investigated in detail. The evaluation of potential tumor markers should allow for the assessment of potency according to pharmaceutical regulations.
METHODS
A panel of 36 tumor-associated antigens and cellular marker proteins was characterized in a total of 133 tumor cell lysates by methods such as ELISA, Western blots, and topological proteomics. The induction of tumor-associated antigen-specific antibodies was demonstrated by immunization in mice.
RESULTS
Tumor heterogeneity was demonstrated: none of the tumor-associated antigens investigated were detectable in each tumor lysate. In parallel, the coincidental presence of potential danger signals was shown for HSP-60 and HSP-70. The presence of both antigen and danger signal allowed a successful induction of an immune response in a murine model.
CONCLUSION
The verified tumor heterogeneity indicates the need for a multi-epitope approach for the successful immunotherapy in renal cell carcinoma.
目的
对一种已成功用于肾细胞癌免疫治疗的自体肿瘤疫苗进行详细研究。对潜在肿瘤标志物的评估应能根据药品法规评估效力。
方法
通过酶联免疫吸附测定（ELISA）、蛋白质免疫印迹法和拓扑蛋白质组学等方法，对总共133份肿瘤细胞裂解物中的36种肿瘤相关抗原和细胞标志物蛋白进行了表征。通过在小鼠体内免疫证明了肿瘤相关抗原特异性抗体的诱导。
结果
证明了肿瘤异质性：在每份肿瘤裂解物中均未检测到所研究的肿瘤相关抗原。同时，显示热休克蛋白60（HSP - 60）和热休克蛋白70（HSP - 70）同时存在潜在危险信号。抗原和危险信号的同时存在使得在小鼠模型中成功诱导了免疫反应。
结论
已证实的肿瘤异质性表明，在肾细胞癌的成功免疫治疗中需要采用多表位方法。
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