美国斯坦福大学Carolyn R. Bertozzi小组开发出抗体-凝集素嵌合体用于糖免疫检查点阻断。2025年12月16日，国际知名学术期刊《自然—生物技术》发表了这一成果。

小组描述了抗体-凝集素嵌合体（AbLecs），一种用于糖免疫检查点阻断的模块化系统。AbLecs是双特异性抗体样分子，包括细胞靶向抗体结构域和凝集素“诱饵受体”结构域，可直接结合聚糖并阻断其与抑制性凝集素受体结合的能力。AbLecs增强了原代人免疫细胞在体外对癌细胞的破坏，并在人源化的免疫活性小鼠模型中减轻了肿瘤负担，优于大多数现有的治疗方法和组合。通过靶向免疫调节的不同轴，AbLecs与已建立的免疫检查点的封锁协同作用。AbLecs可以很容易地设计成针对许多肿瘤和免疫细胞亚群以及糖免疫检查点，它们代表了癌症免疫治疗的潜在模式。

据介绍，尽管检查点阻断免疫疗法具有治疗潜力，但许多患者仍然对现有治疗无反应。糖免疫检查点涉及细胞表面聚糖与凝集素或聚糖结合免疫受体的相互作用，已成为癌症免疫逃避和治疗耐药的重要机制。

附：英文原文

Title: Antibody-lectin chimeras for glyco-immune checkpoint blockade

Author: Stark, Jessica C., Gray, Melissa A., Ibarlucea-Benitez, Itziar, Lustig, Marta, Bond, Annalise, Cho, Brian, Govil, Ishika, Luu, Tran, Priestley, Megan J., Veth, Tim S., Errington, Wesley J., Bruncsics, Bence, Ribi, Mikaela K., Williams, Leo A., Sarkar, Casim A., Wisnovsky, Simon, Riley, Nicholas M., Morrissey, Meghan A., Valerius, Thomas, Ravetch, Jeffrey V., Bertozzi, Carolyn R.

Issue&Volume: 2025-12-16

Abstract: Despite the curative potential of checkpoint blockade immunotherapy, many patients remain unresponsive to existing treatments. Glyco-immune checkpoints, which involve interactions of cell-surface glycans with lectin, or glycan-binding, immunoreceptors, have emerged as prominent mechanisms of immune evasion and therapeutic resistance in cancer. Here, we describe antibody-lectin chimeras (AbLecs), a modular system for glyco-immune checkpoint blockade. AbLecs are bispecific antibody-like molecules comprising a cell-targeting antibody domain and a lectin ‘decoy receptor’ domain that directly binds glycans and blocks their ability to engage inhibitory lectin receptors. AbLecs potentiate cancer cell destruction by primary human immune cells in vitro and reduce tumour burden in a humanized, immunocompetent mouse model, outperforming most existing therapies and combinations tested. By targeting a distinct axis of immunological regulation, AbLecs synergize with blockade of established immune checkpoints. AbLecs can be readily designed to target numerous tumours and immune cell subsets as well as glyco-immune checkpoints, thus representing a potential modality for cancer immunotherapy.

DOI: 10.1038/s41587-025-02884-6

Source: https://www.nature.com/articles/s41587-025-02884-6