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| Home > Publications database > Targeting NKG2DL with Bispecific NKG2D-CD16 and NKG2D-CD3 Fusion Proteins on Triple-Negative Breast Cancer. |
| Home > Publications database > Targeting NKG2DL with Bispecific NKG2D-CD16 and NKG2D-CD3 Fusion Proteins on Triple-Negative Breast Cancer. |
| Journal Article | DKFZ-2023-01854 |
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2023
Molecular Diversity Preservation International
Basel
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Please use a persistent id in citations: doi:10.3390/ijms241713156
Abstract: Triple-negative breast cancer (TNBC) is a particularly aggressive subtype of breast cancer with a poor response rate to conventional systemic treatment and high relapse rates. Members of the natural killer group 2D ligand (NKG2DL) family are expressed on cancer cells but are typically absent from healthy tissues; thus, they are promising tumor antigens for novel immunotherapeutic approaches. We developed bispecific fusion proteins (BFPs) consisting of the NKG2D receptor domain targeting multiple NKG2DLs, fused to either anti-CD3 (NKG2D-CD3) or anti-CD16 (NKG2D-CD16) Fab fragments. First, we characterized the expression of the NKG2DLs (MICA, MICB, ULBP1-4) on TNBC cell lines and observed the highest surface expression for MICA and ULBP2. Targeting TNBC cells with NKG2D-CD3/CD16 efficiently activated both NK and T cells, leading to their degranulation and cytokine release and lysis of TNBC cells. Furthermore, PBMCs from TNBC patients currently undergoing chemotherapy showed significantly higher NK and T cell activation and tumor cell lysis when stimulated with NKG2D-CD3/CD16. In conclusions, BFPs activate and direct the NK and T cells of healthy and TNBC patients against TNBC cells, leading to efficient eradication of tumor cells. Therefore, NKG2D-based NK and T cell engagers could be a valuable addition to the treatment options for TNBC patients.
Keyword(s): Humans (MeSH) ; Triple Negative Breast Neoplasms: drug therapy (MeSH) ; Triple Negative Breast Neoplasms: genetics (MeSH) ; NK Cell Lectin-Like Receptor Subfamily K: genetics (MeSH) ; Ligands (MeSH) ; Administration, Cutaneous (MeSH) ; Aggression (MeSH) ; NK cell ; NKG2D ; T cell ; TNBC ; bispecific ; breast cancer ; fusion protein ; immunotherapy ; NK Cell Lectin-Like Receptor Subfamily K ; Ligands
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