An effective vaccine strategy protective against antigenically distinct tumor variants (Retracted article. See vol. 70, pg. 9528, 2010)
An effective vaccine strategy protective against antigenically distinct tumor variants (Retracted article. See vol. 70, pg. 9528, 2010)
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DOI：
10.1158/0008-5472.can-07-5937
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发表时间：
2008-04-01
期刊：
影响因子：
11.2
通讯作者：
Pease, Larry R.
中科院分区：
文献类型：
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作者：
Pavelko, Kevin D.;Heckman, Karin L.;Pease, Larry R.
抗原性不同的肿瘤变异体可以出现在响应固有的选择性压力。宿主-肿瘤相互作用。成功的免疫策略的发展可能受到这些不同抗原谱的限制。使用免疫调节剂B7-DC XAb激活对肿瘤相关抗原特异性的溶细胞性T细胞，我们发现由活肿瘤引起的免疫应答的特异性不同于由来自相同肿瘤的可溶性蛋白引起的应答的特异性。值得注意的是，尽管针对B16黑色素瘤和EL 4胸腺淋巴瘤肿瘤的活变体产生的诱导的抗肿瘤免疫对攻击中使用的原始肿瘤变体具有高度特异性，但使用源自肿瘤裂解物的可溶性蛋白产生的免疫具有广泛的反应性，识别攻击肿瘤以及抗原性不同的变体。使用活肿瘤和肿瘤裂解物疫苗检测的抗原可以在生物化学上区分，表明它们在结构上不同。我们表明，使用肿瘤细胞裂解物中存在的抗原的疫苗诱导保护性免疫，对远亲肿瘤变体具有强记忆。肿瘤变异体之间共享的一类抗原的存在为疫苗开发提供了有吸引力的靶点。
Antigenically distinct tumor variants can emerge in response to selective pressures inherent to. host-tumor interactions. The development of successful immunotherapeutic strategies can be limited by these disparate antigenic profiles. Using the immunomodulator B7-DC XAb to activate cytolytic T cells specific for tumor-associated antigens, we found that the specificity of immune responses elicited by live tumors are distinct from the specificity of the responses elicited by soluble proteins derived from the same tumors. Remarkably, whereas the induced antitumor immunity generated against live variants of the B16 melanoma and EL4 thymic lymphoma tumors were highly specific for the original tumor variant used in the challenge, immunity generated using soluble proteins derived from tumor lysates was broadly reactive, recognizing the challenge tumor, as well as antigenically distinct variants. The antigens detected using live tumor and tumor lysate vaccines could be distinguished biochemically, demonstrating that they are structurally distinct. We show that vaccines using antigens present in tumor cell lysates induce protective immunity with strong memory against distantly related tumor variants. The existence of a class of antigens shared among tumor variants provides an attractive target for vaccine development.