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001-es BibID:	BIBFORM114079
035-os BibID:	(cikkazonosító)e64485 (WoS)001073487400016 (Scopus)85168335908
Első szerző:	Guti Eliza (Molekuláris biológus)
Cím:	High-Content Screening Assay for the Identification of Antibody-Dependent Cellular Cytotoxicity Modifying Compounds / Eliza Guti, Ákos Máté Bede, Csongor Váróczy, Csaba Hegedűs, Máté Á. Demény, László Virág
Dátum:	2023
ISSN:	1940-087X
Megjegyzések:	Immunotherapy with antigen-specific antibodies or immune checkpoint inhibitors has revolutionized the therapy of breast cancer. Breast cancer cells expressing the epidermal growth factor receptor HER2 can be targeted by the anti-HER-2 antibody trastuzumab. Antibody-dependent cellular cytotoxicity (ADCC) is an important mechanism implicated in the antitumor action of HER-2. Trastuzumab bound to cancer cells can be recognized by the Fc receptors of ADCC effector cells (e.g., natural killer (NK) cells, macrophages, and granulocytes), triggering the cytotoxic activity of these immune cells leading to cancer cell death. We set out to develop an image-based assay for the quantification of ADCC to identify novel ADCC modulator compounds by high-content screening. In the assay, HER2 overexpressing JIMT-1 breast cancer cells are co-cultured with NK-92 cells in the presence of trastuzumab, and target cell death is quantified by automated microscopy and quantitative image analysis. Target cells are distinguished from effector cells based on their EGFP fluorescence. We show how compound libraries can be tested in the assay to identify ADCC modulator drugs. For this purpose, a compound library test plate was set up using randomly selected fine chemicals off the lab shelf. Three microtubule destabilizing compounds (colchicine, vincristine, podophyllotoxin) expected to interfere with NK cell migration and degranulation were also included in the test library. The test screen identified all three positive control compounds as hits proving the suitability of the method to identify ADCC-modifying drugs in a chemical library. With this assay, compound library screens can be performed to identify ADCC-enhancing compounds that could be used as adjuvant therapeutic agents for the treatment of patients receiving anticancer immunotherapies. In addition, the method can also be used to identify any undesirable ADCC-inhibiting side effects of therapeutic drugs taken by cancer patients for different indications.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk
Megjelenés:	Journal of Visualized Experiments. - 198 (2023), p. 1-12. -
További szerzők:	Bede Ákos Máté Váróczy Csongor Hegedűs Csaba (1980-) (biokémikus, molekuláris biológus) Demény Máté Ágoston (1976-) (molekuláris biológus) Virág László (1965-) (biokémikus, sejtbiológus, farmakológus)
Pályázati támogatás:	GINOP-2.3.2-15-2016-00020 GINOP GINOP-2.3.2-15-2016-00048 GINOP
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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