Boston Children's Hospital, Harvard Medical School, Boston, MA, United States.
Department of Cell and Chemical Biology, Leiden University Medical Centre, Leiden, Netherlands.
Front Immunol. 2024 Mar 14;15:1368586. doi: 10.3389/fimmu.2024.1368586. eCollection 2024.
MICA and MICB are Class I MHC-related glycoproteins that are upregulated on the surface of cells in response to stress, for instance due to infection or malignant transformation. MICA/B are ligands for NKG2D, an activating receptor on NK cells, CD8 T cells, and γδ T cells. Upon engagement of MICA/B with NKG2D, these cytotoxic cells eradicate MICA/B-positive targets. MICA is frequently overexpressed on the surface of cancer cells of epithelial and hematopoietic origin. Here, we created nanobodies that recognize MICA. Nanobodies, or VHHs, are the recombinantly expressed variable regions of camelid heavy chain-only immunoglobulins. They retain the capacity of antigen recognition but are characterized by their stability and ease of production. The nanobodies described here detect surface-disposed MICA on cancer cells by flow cytometry and can be used therapeutically as nanobody-drug conjugates when fused to the Maytansine derivative DM1. The nanobody-DM1 conjugate selectively kills MICA positive tumor cells
MICA 和 MICB 是 I 类 MHC 相关糖蛋白，在受到应激（例如感染或恶性转化）时会在细胞表面上调。MICA/B 是 NK 细胞、CD8 T 细胞和γδ T 细胞上激活受体 NKG2D 的配体。MICA/B 与 NKG2D 结合后，这些细胞毒性细胞会消灭 MICA/B 阳性靶标。MICA 在上皮来源和造血来源的癌细胞表面经常过表达。在这里，我们创建了识别 MICA 的纳米抗体。纳米抗体，或 VHHs，是重链仅免疫球蛋白的重组表达可变区。它们保留抗原识别能力，但具有稳定性和易于生产的特点。这里描述的纳米抗体通过流式细胞术检测癌细胞表面的 MICA，并可与美登素衍生物 DM1 融合，作为纳米抗体-药物偶联物用于治疗。纳米抗体-DM1 缀合物选择性杀伤 MICA 阳性肿瘤细胞
