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发明公开
CN110582509A 使用具有多特异性的嵌合T细胞受体蛋白治疗癌症 审中-实审

使用具有多特异性的嵌合T细胞受体蛋白治疗癌症
摘要：
本发明的特征在于嵌合CD3蛋白用来调制T细胞受体(TCR)信号传导的用途。具体地，本发明部分地基于以下发现：在一种或多种同源抗原存在的情况下，其细胞外结构域中的全部或大部分与多于一个抗原结合结构域融合的多种嵌合CD3蛋白(例如CD3δ、CD3γ、和CD3ε)可以活化TCR。本发明进一步基于以下观察：通过在嵌合分子的细胞内部分中包含共刺激结构域，可以加强以上嵌合蛋白。因此，本发明的工程化的信号传导复合物的优选元件包括多于一个抗原结合结构域、源自以上CD3蛋白的细胞外结构域、和细胞内共刺激结构域。
摘要（英）：

The present invention features the use of chimeric CD3 proteins to modulate T cell Receptor (TCR) signaling. Specifically, the invention is based, in part, on the discovery that multiple chimeric CD3proteins (e.g., CD3delta, CD3gamma, and CD3 epsilon) having all or most of their extracellular domain fused to more than one antigen binding domain can activate the TCR in the presence of one or morecognate antigens. The invention is further based on the observation that the above chimeric proteins can be potentiated through the inclusion of a co-stimulatory domain in the intracellular portion ofthe chimeric molecule. Thus, the preferred elements of the engineered signaling complexes of the invention include more than one antigen binding domain, an extracellular domain derived from one of the above CD3 proteins, and an intracellular co-stimulatory domain.

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