Glycan Structures in Osteosarcoma as Targets for Lectin-Based Chimeric Antigen Receptor Immunotherapy

被引：1

作者：

Prasse, Nele ^{[1
]}

Wessolowski, Charlotte ^{[1
]}

Mueller, Ingo ^{[1
,2
]}

Cornils, Kerstin ^{[1
,2
]}

Franke, Anna-Katharina ^{[1
,2
]}

机构：

[1] Res Inst Childrens Canc Ctr Hamburg, D-20251 Hamburg, Germany

[2] Univ Med Ctr Hamburg Eppendorf, Div Pediat Stem Cell Transplantat & Immunol, Clin Pediat Hematol & Oncol, D-20251 Hamburg, Germany

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2024年 / 25卷 / 10期

关键词：

Tn/STn antigen; chimeric antigen receptor; immunotherapy; osteosarcoma; CD301; (MGL; CLEC10A); immune checkpoint inhibition; GALACTOSE/N-ACETYLGALACTOSAMINE; T-CELLS; MACROPHAGE; RECOGNITION; EXPRESSION; BINDING;

D O I：

10.3390/ijms25105344

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页数：11

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