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GENE SIGNATURES AND METHOD FOR PREDICTING RESPONSE TO PD-1 ANTAGONISTS AND CTLA-4 ANTAGONISTS, AND COMBINATION THEREOF

机译:预测PD-1拮抗剂和CTLA-4拮抗剂反应的基因标志,方法及其组合

摘要

The present invention relates to the field of cancer, more particularly to the field of immunotherapy and gene signatures. Provided are two specific and distinct gene signatures, namely a Response Immune Signal (RIS) gene signature and a Stromal Immune Signal (SIS) gene signature, which can be used as biomarkers to accurately predict the response of a cancer subject to treatment with a PD-1 antagonist (e.g., PD-1 antibody) and/or a CTLA-4 antagonist (e.g., CTLA-4 antibody). In particular, it was found that the RIS and SIS gene signatures of the invention may be used in combination to predict the response of a cancer subject to treatment with a combination therapy consisting of a PD-1 antagonist (e.g., PD-1 antibody) and a CTLA-4 antagonist (e.g., CTLA-4 antibody). The gene signatures of the invention may be advantageously used in methods for treating cancer, such as melanoma, and to help devise treatment strategies best suited to individual patients (e.g., to achieve personalized therapy, and spare patients from undesired side effects, e.g., toxicity).
机译:本发明涉及癌症领域,更具体地涉及免疫疗法和基因签名领域。提供了两个特定且不同的基因签名,即响应免疫信号(RIS)基因签名和基质免疫信号(SIS)基因签名,它们可以用作生物标记物,以准确预测受PD治疗的癌症的反应-1拮抗剂(例如PD-1抗体)和/或CTLA-4拮抗剂(例如CTLA-4抗体)。特别地,发现本发明的RIS和SIS基因标记可以组合使用以预测受由PD-1拮抗剂(例如,PD-1抗体)组成的联合疗法治疗的癌症的反应和CTLA-4拮抗剂(例如CTLA-4抗体)。本发明的基因标记可有利地用于治疗诸如黑素瘤的癌症的方法中,并帮助设计出最适合个体患者的治疗策略(例如,实现个性化治疗,并使患者免受不良副作用,例如毒性)的伤害。 )。

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