Glycan Structures in Osteosarcoma as Targets for Lectin-Based Chimeric Antigen Receptor Immunotherapy
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Glycan Structures in Osteosarcoma as Targets for Lectin-Based Chimeric Antigen Receptor Immunotherapy. / Prasse, Nele; Wessolowski, Charlotte; Müller, Ingo; Cornils, Kerstin; Franke, Anna-Katharina.
In: INT J MOL SCI, Vol. 25, No. 10, 5344, 14.05.2024.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Glycan Structures in Osteosarcoma as Targets for Lectin-Based Chimeric Antigen Receptor Immunotherapy
AU - Prasse, Nele
AU - Wessolowski, Charlotte
AU - Müller, Ingo
AU - Cornils, Kerstin
AU - Franke, Anna-Katharina
PY - 2024/5/14
Y1 - 2024/5/14
N2 - 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.
AB - 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.
KW - Osteosarcoma/therapy
KW - Humans
KW - Bone Neoplasms/immunology
KW - Immunotherapy/methods
KW - Lectins, C-Type/metabolism
KW - Polysaccharides/metabolism
KW - Receptors, Chimeric Antigen/metabolism
KW - Cell Line, Tumor
KW - Female
KW - Male
KW - Child
KW - Adolescent
KW - Receptors, Immunologic/metabolism
U2 - 10.3390/ijms25105344
DO - 10.3390/ijms25105344
M3 - SCORING: Journal article
C2 - 38791381
VL - 25
JO - INT J MOL SCI
JF - INT J MOL SCI
SN - 1661-6596
IS - 10
M1 - 5344
ER -