Department of Chemistry, University of Zurich, 8057, Zurich, Switzerland.
Chembiochem. 2022 Aug 3;23(15):e202200125. doi: 10.1002/cbic.202200125. Epub 2022 Jun 20.
Stimulation of the body's immune system toward tumor cells is now well recognized as a promising strategy in cancer therapy. Just behind cell therapy and monoclonal antibodies, small molecule-based strategies are receiving growing attention as alternatives to direct immune response against tumor cells. However, the development of small-molecule approaches to modulate the balance between stimulatory immune factors and suppressive factors in a targeted way remains a challenge. Here, we report the cell surface functionalization of LS174T cancer cells with an abiotic hapten to recruit antibodies to the cell surface. Metabolic glycoengineering followed by covalent reaction with the hapten results in antibody recognition of the target cells. Microscopy and flow cytometry studies provide compelling evidence that metabolic glycoengineering and small molecule stimulators can be combined to direct antibody recognition.
刺激机体的免疫系统对肿瘤细胞的反应，目前已被充分认可为癌症治疗中一种很有前途的策略。继细胞疗法和单克隆抗体之后，小分子策略作为直接针对肿瘤细胞的免疫反应的替代方法，受到越来越多的关注。然而，开发小分子方法来有针对性地调节刺激免疫因子和抑制因子之间的平衡仍然是一个挑战。在这里，我们报告了用非生物半抗原对 LS174T 癌细胞进行细胞表面功能化，以招募抗体到细胞表面。代谢糖基工程，然后与半抗原发生共价反应，导致抗体识别靶细胞。显微镜和流式细胞术研究提供了有力的证据，证明代谢糖基工程和小分子刺激物可以结合起来，指导抗体识别。
