CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
骨肉瘤中的聚糖结构作为基于凝集素的嵌合抗原受体免疫治疗的靶点
英文原题：Glycan Structures in Osteosarcoma as Targets for Lectin-Based Chimeric Antigen Receptor Immunotherapy.
查看英文原题
Glycan Structures in Osteosarcoma as Targets for Lectin-Based Chimeric Antigen Receptor Immunotherapy.
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中文摘要
骨肉瘤是一种主要影响儿童和年轻人的骨癌。局限性骨肉瘤的总体5年生存率为70-75%，但复发或转移性肿瘤患者仅为20-30%。为了研究潜在的糖基靶向结构用于免疫治疗，我们用重组C型凝集素CD301（MGL，CLEC10A）对原发性骨肉瘤进行染色，观察到26%的肿瘤呈现中度至强染色。表达CD301-CAR的NK92细胞在体外识别并清除了骨肉瘤细胞。细胞毒性活性测定与脱颗粒和细胞因子释放测定相关。与针对免疫检查点TIGIT（T细胞免疫受体含Ig和ITIM结构域）的抑制性抗体联合使用显示出有前景的额外效果。总体而言，本研究首次展示了CD301配体在骨肉瘤组织中的表达，并证明了它们可作为基于凝集素的免疫治疗的潜在靶结构。
展开英文摘要原文
Osteosarcoma is a type of bone cancer that primarily affects children and young adults. The overall 5-year survival rate for localized osteosarcoma is 70-75%, but it is only 20-30% for patients with relapsed or metastatic tumors. To investigate potential glycan-targeting structures for immunotherapy, we stained primary osteosarcomas with recombinant C-type lectin CD301 (MGL, CLEC10A) and observed moderate to strong staining on 26% of the tumors.
NK92 cells expressing a CD301-CAR recognized and eliminated osteosarcoma cells in vitro. Cytotoxic activity assays correlated with degranulation and cytokine release assays. Combination with an inhibitory antibody against the immune checkpoint TIGIT (T-cell immunoreceptor with lg and ITIM domains) showed promising additional effects.
Overall, this study showed, for the first time, the expression of CD301 ligands in osteosarcoma tissue and demonstrated their use as potential target structures for lectin-based immunotherapy.
论文信息
- 作者
- Prasse N、Wessolowski C、Müller I、Cornils K、Franke AK
- 单位
- Research Institute Children's Cancer Center Hamburg, 20251 Hamburg, Germany.Germany
- 期刊
- International journal of molecular sciences2024 May 14
- 原文标识
- PubMed 38791381 · DOI 10.3390/ijms25105344