研究人员在《自然—医学》（Nature Medicine）上发表一篇题为“Multipeptide immune response to cancer vaccine IMA901 after single-dose cyclophosphamide associates with longer patient survival”的论文，指出晚期肾癌患者在注射IMA901这种首个针对肾癌的治疗性多肽疫苗后会表达出一种特定抗原。
首个治疗性疫苗有望对付肾癌
肾癌和相关疫苗介绍
肾癌起源于泌尿小管上皮，约占成人恶性肿瘤的80%-90%, 是成人最常见的肾脏肿瘤。男女之比约为2：1，可见于各个年龄段，高发年龄50-70岁。随着体检的普及，越来越多的早期肾癌得到了及时诊断。不吸烟及避免肥胖是预防肾癌发生的重要方法。
治疗性疫苗与传统预防性疫苗的不同之处在于其并非在患病前注射，而是作为一种治疗手段将药物送入已患病人体内。治疗性癌症疫苗的开发目前仍是一项挑战，很多关键问题还未能得到解决，比如，如何确定合适的目标肿瘤抗原和能够可预测患者治疗反应的生物标记等。
IMA901疫苗在肾癌治疗的应用
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。
Harpreet Singh-Jasuja等人对表达出人体白细胞抗原HLA-A的晚期肾癌患者进行组织取样，找到一种特殊的多肽并开发出一种疫苗IMA901。这种疫苗能够在HLA-A抗原表达的患者体内诱发免疫应答。在第一阶段研究中，IMA901诱发了与调节性T细胞低数量有关的多重T细胞免疫应答，T细胞通常是对免疫应答起抑制作用的。研究人员还发现，如果患者在注射IMA901之前，就注射单剂量的环磷酰胺——一种被用来治疗多种癌症的药物——的话，其体内的调节性T细胞数量会更少，从而延长患者的存活时间。至于该疫苗能否让更多人受益，还需要通过进一步的临床测试作出评估。
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。
Multipeptide immune response to cancer vaccine IMA901 after single-dose cyclophosphamide associates with longer patient survival
Steffen Walter, Toni Weinschenk, Arnulf Stenzl, Romuald Zdrojowy, Anna Pluzanska, Cezary Szczylik, Michael Staehler, Wolfram Brugger, Pierre-Yves Dietrich, Regina Mendrzyk, Norbert Hilf, Oliver Schoor, Jens Fritsche, Andrea Mahr, Dominik Maurer, Verona Vass, Claudia Trautwein, Peter Lewandrowski, Christian Flohr, Heike Pohla, Janusz J Stanczak, Vincenzo Bronte, Susanna Mandruzzato, Tilo Biedermann, Graham Pawelec, Evelyna Derhovanessian, Hisakazu Y
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.
文献链接： Multipeptide immune response to cancer vaccine IMA901 after single-dose cyclophosphamide associates with longer patient survival
