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@ARTICLE{Kaidun:282728,
author = {P. Kaidun$^*$ and S. Holzmayer$^*$ and S. M. Greiner$^*$
and A. Seller$^*$ and C. M. Tegeler and I. Hagelstein$^*$
and J. Mauermann$^*$ and T. Engler and A. Koch and A. D.
Hartkopf and H. Salih$^*$ and M. Märklin$^*$},
title = {{T}argeting {NKG}2{DL} with {B}ispecific {NKG}2{D}-{CD}16
and {NKG}2{D}-{CD}3 {F}usion {P}roteins on
{T}riple-{N}egative {B}reast {C}ancer.},
journal = {International journal of molecular sciences},
volume = {24},
number = {17},
issn = {1422-0067},
address = {Basel},
publisher = {Molecular Diversity Preservation International},
reportid = {DKFZ-2023-01854},
pages = {13156},
year = {2023},
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.},
keywords = {Humans / Triple Negative Breast Neoplasms: drug therapy /
Triple Negative Breast Neoplasms: genetics / NK Cell
Lectin-Like Receptor Subfamily K: genetics / Ligands /
Administration, Cutaneous / Aggression / NK cell (Other) /
NKG2D (Other) / T cell (Other) / TNBC (Other) / bispecific
(Other) / breast cancer (Other) / fusion protein (Other) /
immunotherapy (Other) / NK Cell Lectin-Like Receptor
Subfamily K (NLM Chemicals) / Ligands (NLM Chemicals)},
cin = {TU01},
ddc = {540},
cid = {I:(DE-He78)TU01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37685962},
pmc = {pmc:PMC10487695},
doi = {10.3390/ijms241713156},
url = {https://inrepo02.dkfz.de/record/282728},
}