Nat Med：新研究显示IMA901肾癌疫苗优于化疗

近日，来自蒂宾根大学等处的研究者发表了两项实验研究结果，揭示了肾癌的疫苗IMA901的部分研究成果，相关研究结果已于近日刊登在了国际著名杂志Nature Medicine上。IMA901常被用来治疗肾癌患者，由10种合成性肿瘤相关多肽(TUMAPs)组成，可以激活机体杀伤T细胞抵御肿瘤的能力。不像化学疗法，以免疫系统为靶点的新疗法可以动员免疫系统来攻击癌症，研究揭示了这种抵御癌症的免疫活性法非常成功，并且可以延长患者寿命，而且副作用比较小。

研究者Hans等表示，这项研究工作是癌症免疫疗法的里程碑，以前所有的用药疗法在抑制肾脏肿瘤生长上有明确的改进，但是这并不能使得肾癌患者寿命延长，而且不能治愈疾病。

这项研究揭示了肾癌患者可以携带有针对两个或更多肿瘤相关的肽类，这样免疫反应和临床效应就可以明确的联系起来了。这就再次肯定了癌症疗法可以在未来通过激活免疫效用来实现。

研究论文中，研究者同样也描述了他们发现了生物标记物，在病人接受IMA901之后如何延长其生存可以给予一个精确的预测。一项超过300个潜在标志物的分析揭示了患者机体的免疫效应以及IMA901治疗后病人生命的延长效应。

编译自：Kidney Cancer Vaccine Successful in Clinical Trials

doi:10.1038/nm.2883
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Multipeptide immune response to cancer vaccine IMA901 after single-dose cyclophosphamide associates with longer patient survival

Steffen Walter,1, 21 Toni Weinschenk,1, 21 Arnulf Stenzl,2 Romuald Zdrojowy,3 Anna Pluzanska,4 Cezary Szczylik,5 Michael Staehler,6 Wolfram Brugger,7 Pierre-Yves Dietrich,8 Regina Mendrzyk,1 Norbert Hilf,1 Oliver Schoor,1 Jens Fritsche,1 Andrea Mahr,1 Dominik Maurer,1 Verona Vass,1 Claudia Trautwein,1 Peter Lewandrowski,1 Christian Flohr,1 Heike Pohla,9, 10 Janusz J Stanczak,11 Vincenzo Bronte,12 Susanna Mandruzzato,13, 14 Tilo Biedermann,15 Graham Pawelec,16 Evelyna Derhovanessian,16 Hisakazu Yamagishi,17 Tsuneharu Miki,18 Fumiya Hongo,18 Natsuki Takaha,18 Kosei Hirakawa,19 Hiroaki Tanaka,19 Stefan Stevanovic,20 Jürgen Frisch,1 Andrea Mayer-Mokler,1 Alexandra Kirner,1 Hans-Georg Rammensee,20 Carsten Reinhardt1, 21 & Harpreet Singh-Jasuja1, 21 et al.

IMA901 is the first therapeutic vaccine for renal cell cancer (RCC) consisting of multiple tumor-associated peptides (TUMAPs) confirmed to be naturally presented in human cancer tissue. We treated a total of 96 human leukocyte antigen A (HLA-A)*02+ subjects with advanced RCC with IMA901 in two consecutive studies. In the phase 1 study, the T cell responses of the patients to multiple TUMAPs were associated with better disease control and lower numbers of prevaccine forkhead box P3 (FOXP3)+ regulatory T (Treg) cells. The randomized phase 2 trial showed that a single dose of cyclophosphamide reduced the number of Treg cells and confirmed that immune responses to multiple TUMAPs were associated with longer overall survival. Furthermore, among six predefined populations of myeloid-derived suppressor cells, two were prognostic for overall survival, and among over 300 serum biomarkers, we identified apolipoprotein A-I (APOA1) and chemokine (C-C motif) ligand 17 (CCL17) as being predictive for both immune response to IMA901 and overall survival. A randomized phase 3 study to determine the clinical benefit of treatment with IMA901 is ongoing.