Combinatorial Fc modifications for complementary antibody functionality

Yannic C. Bartsch

doi:10.1080/19420862.2025.2465391

2025-02-14

Douglas A. Lauffenburger

Boris Jülg *

DOI：10.1080/19420862.2025.2465391

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摘要

En 中文

治疗性单克隆抗体（mAbs）可通过Fc工程进行功能增强。为确定具有不同Fc修饰的mAb对是否可组合以实现功能互补，我们研究了两个HIV-1 mAb库的体外活性，每个库均配备60种工程化Fc变体。我们的发现表明，Fc工程对Fc功能的影响取决于特定的Fab克隆。值得注意的是，相同Fab特异性的Fc变体组合在功能广度上的增强有限，而涉及两种不同Fabs的组合则显示出更大的提升。这表明战略性地选择互补的Fc修饰可增强功能活性和广度。此外，虽然某些Fc变体组合表现出功能叠加效应，但其他组合则产生不利影响，提示Fc突变的结局难以预测。综合来看，这些结果为mAb组合中互补Fc修饰的潜力提供了初步证据。未来的研究将有助于确定最大化体内疗效的最优Fc修饰。

Keyword:

Broadly functional antibodies

complimentary combinations

Fc-modifications

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7.3

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a ragon institute of mass general

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Massachusetts Institute of Technology

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