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Treating human cancers with heat shock protein-peptide complexes: the road ahead.

机译:用热激蛋白-肽复合物治疗人类癌症:未来之路。

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BACKGROUND: Heat shock proteins (HSPs) chaperone a wide array of peptides generated in cells. Association of HSPs with peptides is critical for loading of MHC I with epitopes, and has been suggested to be essential for cross-presentation. HSP-peptide complexes purified from cancer cells have been shown to chaperone tumor-specific antigenic epitopes, and have been used in experimental immunotherapy of human cancers. Two randomized Phase III trials have been completed recently. OBJECTIVE: To summarize the lessons learned from the Phase III studies and to opine on the path forward. RESULTS/CONCLUSION: Immunization of human subjects with HSP-peptide complexes derived from autologous tumors mediates substantial clinical benefit in subjects with relatively early stage disease, consistent with results seen in animal models of cancer, and with an immunological mechanism of action. Additional clinical studies are essential for further development of this personalized medicine.
机译:背景:热激蛋白(HSP)可以陪伴细胞中产生的多种肽。 HSP与肽的缔合对于将MHC I上载抗原决定簇至关重要,并且已被建议对于交叉展示至关重要。从癌细胞中纯化的HSP肽复合物已显示出伴侣分子肿瘤特异性抗原表位,并已用于人类癌症的实验性免疫治疗。最近完成了两项随机的III期临床试验。目的:总结从第三阶段研究中汲取的经验教训,并展望前进的方向。结果/结论:用自体肿瘤衍生的HSP-肽复合物对人类受试者进行免疫,可在患有相对早期疾病的受试者中发挥实质性的临床益处,与癌症动物模型中观察到的结果一致,并具有免疫作用机制。其他临床研究对于进一步开发这种个性化药物至关重要。

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