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 journalSCORING: Journal articleResearchpeer-review

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@article{09c35bf3d60248c29262af3802c11ee1,
title = "Glycan Structures in Osteosarcoma as Targets for Lectin-Based Chimeric Antigen Receptor Immunotherapy",
abstract = "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.",
keywords = "Osteosarcoma/therapy, Humans, Bone Neoplasms/immunology, Immunotherapy/methods, Lectins, C-Type/metabolism, Polysaccharides/metabolism, Receptors, Chimeric Antigen/metabolism, Cell Line, Tumor, Female, Male, Child, Adolescent, Receptors, Immunologic/metabolism",
author = "Nele Prasse and Charlotte Wessolowski and Ingo M{\"u}ller and Kerstin Cornils and Anna-Katharina Franke",
year = "2024",
month = may,
day = "14",
doi = "10.3390/ijms25105344",
language = "English",
volume = "25",
journal = "INT J MOL SCI",
issn = "1661-6596",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "10",

}

RIS

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 -