CCL

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1.

001-es BibID:BIBFORM006064
035-os BibID:WOS:A1996UY72200007
Első szerző:Bacsó Zsolt (biofizikus)
Cím:Changes in membrane potential of target cells promotes cytotoxic activity of effector T lymphocytes / Zsolt Bacsó, János Matkó, János Szöllősi, Rezső Gáspár, Sándor Damjanovich
Dátum:1996
Megjegyzések:The effector function of CD8+ lymphocytes depends on recognition by the TcR-CD3 complex of an oligopeptide presented by an MHC class I molecule on target cells. Recently it has been shown that MHC class I molecules change their conformation upon depolarization of human B lymphoblastoid JY cells. We studied here the effects of changes in membrane potential of target cells on the function of cytotoxic T lymphocytes (CTL). Selective alterations of plasma membrane potential of JY target cells were achieved by treatments with specific ionophore molecules as well as with Na(+)-K(+)-ATPase inhibitor, while the cytotoxic lymphocytes were not influenced. The plasma membrane was depolarized by gramicidin D and ouabain, while hyperpolarization was induced by valinomycin treatment. Alterations of the resting membrane potential of target cells in both direction resulted in an enhanced cytotoxic activity. The observed changes in cytolytic activities of cytotoxic T effectors may have a more general biological significance, namely apoptotic cells become depolarized after a given time, moreover neoplastic and virus infected cells also frequently show decreased membrane potential. A more efficient recognition of these cells by CTL is supposed to enhance the efficiency of their elimination, as well.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Cytotoxicity,Immunologic
Human
Hungary
immunology
Lymphocytes
Membrane Potentials
Support,Non-U.S.Gov't
T-Lymphocytes
T-Lymphocytes,Cytotoxic
Tumor Cells,Cultured
Valinomycin
egyetemen (Magyarországon) készült közlemény
Megjelenés:Immunology Letters. - 51 : 3 (1996), p. 175-180. -
További szerzők:Matkó János (1952-) (biológus) Szöllősi János (1953-) (biofizikus) Gáspár Rezső (1944-) (biofizikus) Damjanovich Sándor (1936-2017) (biofizikus)
Internet cím:elektronikus változat
DOI
Borító:

2.

001-es BibID:BIBFORM006027
Első szerző:Bene László (biofizikus)
Cím:Lateral organization of the ICAM-1 molecule at the surface of human lymphoblasts : a possible model for its co-distribution with the IL-2 receptor, class I and class II HLA molecules / Bene L., Balázs M., Matkó J., Möst J., Dierich M. P., Szöllösi J., Damjanovich S.
Dátum:1994
Megjegyzések:Lateral distribution of the ICAM-1 molecule and its topological relationship (mutual proximity) to the heavy and light chains of class I HLA molecules, HLA-DR and interleukin-2 receptor alpha-chain (IL-2R alpha) were studied in the plasma membrane of HUT-102B2 T and JY B lymphoblastoid cell lines by the technique of flow cytometric energy transfer (FCET). Effects of adherency and treatments with recombinant interferon-gamma or tumor necrosis factor-alpha on the relative expression level of ICAM-1 to the above cell surface proteins were also investigated. While the cytokines did not significantly affect the ICAM-1 level of either cell line, an increased ICAM-1 expression was found on adherent JY cells. The ICAM-1 expression varied significantly with the cell cycle and culture conditions, as well. The statistical analysis of the differences observed in the energy transfer efficiency histograms resulted in a possible model of lateral co-distribution of these proteins in the plasma membrane. These two-dimensional patterns proved to be different for T and B lymphoma lines. ICAM-1 molecules showed a high degree of self-association on HUT-102B2 (T) cells, while they were mainly expressed as monomers on the surface of JY (B) cells. Both cells showed a significant (ca. 30%) difference between densities of the heavy and light chains of class I HLA antigen, suggesting a substantial amount of beta 2-microglobulin free heavy chains on these cell lines. The class I HLA molecules also showed partial self-association, but on both cell lines. The beta 2-microglobulin and the heavy chain of the class I HLA showed strongly different proximities to the IL-2R alpha, HLA-DR and ICAM-1 molecules, indicating that their orientations relative to the other proteins are dissimilar. IL-2R alpha molecules of the HUT-102B2 (T) cells are located mostly in the vicinity of the beta 2-microglobulin. In contrast, the local density of HLA-DR antigens is higher in the proximity of the heavy chain than in the vicinity of the beta 2-microglobulin. The possible functional significance of these protein patterns is also discussed herein.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
analysis
Antibodies,Monoclonal
B-Lymphocyte Subsets
beta 2-Microglobulin
Cell Adhesion
Cell Adhesion Molecules
Cell Cycle
Cell Line
Energy Transfer
Flow Cytometry
Histocompatibility Antigens Class I
HLA Antigens
HLA-D Antigens
HLA-DR Antigens
Human
Hungary
immunology
Intercellular Adhesion Molecule-1
Interferon Type II
Interleukin-2
Light
physiology
Receptors,Interleukin-2
Support,Non-U.S.Gov't
Support,U.S.Gov't,Non-P.H.S.
T-Lymphocyte Subsets
Tumor Necrosis Factor
Megjelenés:European Journal of Immunology. - 24 : 9 (1994), p. 2115-2123. -
További szerzők:Balázs Margit (1952-) (sejtbiológus, molekuláris genetikus) Matkó János (1952-) (biológus) Most, J. Dierich, Manfred P. Szöllősi János (1953-) (biofizikus) Damjanovich Sándor (1936-2017) (biofizikus)
Internet cím:DOI
Borító:

3.

001-es BibID:BIBFORM006031
Első szerző:Damjanovich Sándor (biofizikus)
Cím:Transmembrane signalling in T cells / Sándor Damjanovich, János Szöllősi, Lajos Trón
Dátum:1992
Megjegyzések:Transmembrane signalling to activate T cells to proliferate and differentiate is a complex multistep process. It is the focus of much current interest, mostly because a selective and well-controlled inhibition of the process will allow regulation, or at least modulation, of the immune response. Here, Sandor Damjanovich and colleagues review the contributions of Hungarian scientists to the understanding of signalling in lymphocytes in particular, and cell activation in general.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Antigens,CD
Antigens,CD2
Antigens,CD45
Antigens,Differentiation,T-Lymphocyte
Antigens,Surface
Calcium
Cell Membrane
Glycoproteins
Histocompatibility Antigens
Human
Hungary
immunology
Immunosuppression
Ion Channels
Lymphocyte Transformation
Lymphocytes
Membrane Glycoproteins
metabolism
Phosphoprotein Phosphatase
Receptors,Immunologic
Signal Transduction
T-Lymphocytes
Megjelenés:Immunology Today. - 13 : 8 (1992), p. A12-A15. -
További szerzők:Szöllősi János (1953-) (biofizikus) Trón Lajos (1941-) (biofizikus)
Internet cím:elektronikus változat
Borító:

4.

001-es BibID:BIBFORM005972
Első szerző:Damjanovich Sándor (biofizikus)
Cím:Dynamic properties of the murine histocompatibility H-2Kk antigen in cytoplasmic membrane / S. Damjanovich, L. Tron, J. Szollosi, L. Matyus, G. Szabo
Dátum:1984
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
analysis
Animal
Antigens,Surface
Biophysics
Cell Membrane
Concanavalin A
Epitopes
Fibroblasts
H-2 Antigens
Human
immunology
Lymphocytes
Lymphoma
metabolism
Mice
Mice,Inbred A
Receptors,Concanavalin A
Rotation
Megjelenés:Molecular Immunology. - 21 : 12 (1984), p. 1151-1155. -
További szerzők:Trón Lajos (1941-) (biofizikus) Szöllősi János (1953-) (biofizikus) Mátyus László (1956-) (biofizikus) Szabó Gábor (1953-) (biofizikus)
Internet cím:elektronikus változat
DOI
Intézményi repozitóriumban (DEA) tárolt változa
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5.

001-es BibID:BIBFORM005968
035-os BibID:(scopus)0023260317
Első szerző:Damjanovich Sándor (biofizikus)
Cím:Cyclosporin depolarizes human lymphocytes : earliest observed effect on cell metabolism / S. Damjanovich, A. Aszalos, S. A. Mulhern, J. Szollosi, M. Balazs, L. Tron, M. J. Fulwyler
Dátum:1987
Megjegyzések:Cyclosporin A (CsA) produced dose-dependent membrane depolarization of human peripheral blood lymphocytes. The phenomenon was investigated applying the membrane potential probe dihexyloxacarbocyanine iodide in a flow cytometer in combination with ionophores, hormones and monoclonal antibodies binding to different subclasses of lymphocytes and the anti-interleukin 2 receptor antibody. Human interferon-gamma abolished the depolarizing effect of cyclosporin on lymphocytes. Interleukin 2 caused depolarization and also enhanced the effect of CsA. OKT4 and OKT8 monoclonal antibodies slightly hindered depolarization by CsA while OKT3, OKT11 and OKIa1 antibodies had no such effect. Valinomycin decreased CsA's effect on the membrane potential while the ionophore A-23187 and ionomycin caused depolarizations that were additive with CsA's. CsA treatment released the isotope from 42K-loaded human lymphocytes in a dose-dependent fashion. CsA addition increased intracellular calcium content. CsA decreased the motional freedom of a spin probe in the membrane, but did not hinder the binding of fluoresceinated antibodies to the cell surface. These results suggest immediate alteration in membrane structure upon CsA treatment, causing potassium leakage and calcium ion uptake. These are the earliest detected effects of CsA on cells so far.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Antibodies,Monoclonal
blood
Calcium
Carbocyanines
Cell Membrane
classification
Cyclosporins
Cytoplasm
Dimethyl Sulfoxide
drug effects
Electron Spin Resonance Spectroscopy
Flow Cytometry
Human
immunology
Interferon Type II
Interleukin-2
Intracellular Membranes
Ion Channels
Ionomycin
Ionophores
Lymphocytes
Membrane Fluidity
Membrane Potentials
metabolism
methods
pharmacology
Potassium
Potassium Radioisotopes
Spectrometry,Fluorescence
ultrastructure
Valinomycin
Megjelenés:European Journal of Immunology. - 17 : 6 (1987), p. 763-768. -
További szerzők:Aszalos Adorján Mulhern, Sally Szöllősi János (1953-) (biofizikus) Balázs Margit (1952-) (sejtbiológus, molekuláris genetikus) Trón Lajos (1941-) (biofizikus) Fulwyler, Mack J.
Internet cím:elektronikus változat
Borító:

6.

001-es BibID:BIBFORM004703
035-os BibID:(scopus)0037013728 (wos)000176059200014
Első szerző:Damjanovich Sándor (biofizikus)
Cím:Does mosaicism of the plasma membrane at molecular and higher hierarchical levels in human lymphocytes carry information on the immediate history of cells? / Damjanovich, S., Matyus, L., Damjanovich, L., Bene, L., Jenei, A., Matko, J., Gaspar, R., Szollosi, J.
Dátum:2002
Megjegyzések:A theoretical analysis of experimental data is presented in this mini-review on non-random homo- and hetero-associations of cell surface receptors, which can be recruited in the plasma membrane or at the surface of the rough endoplasmic reticulum during the protein synthesis. In the latter case, the likely genetic origin of these supramolecular formations is analyzed, contrasting this concept to the mobility of the cell surface proteins. A model is offered which, on the one hand, allows the mobility in a restricted way even among microdomain-confined receptor proteins through 'swapping partners'. On the other hand, the lack of mixing molecular components of protein clusters will be analyzed, when homo-and hetero-associations are studied through cell fusion experiments. The most frequently studied cell surface patterns have included lipid raft organized HLA class I and II, ICAM-1, tetraspan molecules, IL2 and IL15 and other receptors, as well. On the contrary coated pit-associated transferrin receptors would not mix with the above lipid raft associated receptor patterns, although transferrin receptor would readily oligomerize into homo-associates. The functional consequences of these superstructures are also analyzed. On the 30th anniversary of the Singer-Nicolson fluid mosaic membrane model one has to pay tribute to the authors, because of their deep insight emphasizing also the mosaicism of the membranes in general and that of the plasma membrane, in particular.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
analysis
Biophysics
Cell Fusion
Cells
Human
Hungary
Lymphocytes
Proteins
egyetemen (Magyarországon) készült közlemény
Megjelenés:Immunology Letters. - 82 : 1-2 (2002), p. 93-99. -
További szerzők:Mátyus László (1956-) (biofizikus) Damjanovich László (1960-) (általános sebész) Bene László (1963-) (biofizikus) Jenei Attila (1966-) (biofizikus) Matkó János (1952-) (biológus) Gáspár Rezső (1944-) (biofizikus) Szöllősi János (1953-) (biofizikus)
Internet cím:DOI
elektronikus változat
Borító:

7.

001-es BibID:BIBFORM010350
035-os BibID:(scopus)67349251235 (wos)000267233000008
Első szerző:Friedländer Elza (biofizikus)
Cím:Corrigendum to ?ErbB-directed immunotherapy: Antibodies in current practice and promising new agents" [Immunol. Lett. 116/2 (2008) 126-140] / Friedlander, E., Barok, M., Szollosi, J., Vereb, G.
Dátum:2009
ISSN:0165-2478
Tárgyszavak:Orvostudományok Elméleti orvostudományok hozzászólás
folyóiratcikk
Antibodies
Megjelenés:Immunology Letters. - 124 : 1 (2009), p. 55-56. -
További szerzők:Barok Márk (1976-) (biofizikus) Szöllősi János (1953-) (biofizikus) Vereb György (1965-) (absztraktok, könyvfejezetek)
Internet cím:DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

8.

001-es BibID:BIBFORM005181
035-os BibID:(scopus)40149107884 (wos)000255092200005
Első szerző:Friedländer Elza (biofizikus)
Cím:ErbB-directed immunotherapy : antibodies in current practice and promising new agents / Elza Friedländer, Márk Barok, János Szöllősi, György Vereb
Dátum:2008
Megjegyzések:The ErbB family is well known for its significance in oncogenesis. As bad prognostic markers, overexpressed or mutated ErbB1 and ErbB2 have an important role in the molecular diagnosis of various cancers, but as membrane proteins, expressed often selectively in tumor tissues, they can be targeted with kinase inhibitors or therapeutic antibodies. In addition to trastuzumab, the first humanized antibody that was approved for the therapy of solid tumors by the FDA, now many humanized antibodies are in late clinical trials, or already approved. Conjugation of antibodies with radioactive isotopes, cytotoxic agents or liposomes loaded with chemotherapeutic drugs led to improved therapeutic efficiency over their parent "unarmed" antibodies. Novel, engineered antibody derivates with better pharmacodynamic properties are also available and allow the targeting of ErbB1 or ErbB2 positive cancers in a wider patient population. In this review, we discuss the biological and clinical background of ErbB targeting, and describe the most successful antibodies against ErbB1 (cetuximab, panitumumab, matuzumab, nimotuzumab, ICR62, mAb 528, ch806 and MDX-447) and ErbB2 (trastuzumab, pertuzumab, MDX-H210, 2B1, C6.5xscFv(NM3E2), ertumaxomab and FRP-5 derivates) that are in clinical trials or already approved, along with the various relevant conjugation and engineering strategies. Recent data pertinent to the prevalent problem of clinical resistance to treatment with trastuzumab are also discussed.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
agonists
analysis
Animal
Antibodies
Antibody conjugation
Antibody targeted delivery
Apoptosis
Biophysics
Brain
Carcinoma
Cell Line
Cell Proliferation
Cell Survival
Cells
Clinical trial
Cysteine
diagnosis
Dimerization
Down-Regulation
Drug Resistance
EGFR
Endocytosis
Engineered antibody
Epidermal Growth Factor
Epitopes
ErbB1
ErbB2
Fibroblasts
Glioblastoma
Glioma
Human
Humanized antibody
Hungary
In Vitro
Insulin
Membrane Proteins
Mice
Microscopy
Microspheres
Mutation
Necrosis
Paclitaxel
Phenotype
Phosphorylation
Prevalence
Progesterone
Proteins
radiotherapy
Research
Signal Transduction
therapy
toxicity
Trastuzumab resistance
Tumor Necrosis Factor
Tumor therapy/cancer therapy
Tyrosine
Up-Regulation
Megjelenés:Immunology Letters. - 116 : 2 (2008), p. 126-140. -
További szerzők:Barok Márk (1976-) (biofizikus) Szöllősi János (1953-) (biofizikus) Vereb György (1965-) (biofizikus, orvos)
Internet cím:elektronikus változat
DOI
elektronikus változat
Borító:

9.

001-es BibID:BIBFORM060604
035-os BibID:(scopus)0035871630 (wos)000170948300037
Első szerző:Gáspár Rezső (biofizikus)
Cím:Clustering of class I HLA oligomers with CD8 and TCR: three-dimensional models based on fluorescence resonance energy transfer and crystallographic data / Rezső Gáspár Jr., Péter Bagossi, László Bene, János Matkó, János Szöllősi, József Tőzsér, László Fésüs, Thomas A. Waldmann, Sándor Damjanovich
Dátum:2001
Megjegyzések:Fluorescence resonance energy transfer (FRET) data, in accordance with lateral mobility measurements, suggested the existence of class I HLA dimers and oligomers at the surface of live human cells, including the B lymphoblast cell line (JY) used in the present study. Intra- and intermolecular class I HLA epitope distances were measured on JY B cells by FRET using fluorophoreconjugated Ag-binding fragments of mAbs W6/32 and L368 directed against structurally well-characterized heavy and light chain epitopes, respectively. Out-of-plane location of these epitopes relative to the membrane-bound BODIPY-PC (2-(4,4-difluoro-5-(4- phenyl-1,3-butadienyl)-4-bora-3a,4a-diaza-s-indacene-3-pentanoyl)-1-hexadecanoyl-sn-glycero-3-phosphocholine) was also determined by FRET. Computer-simulated docking of crystallographic structures of class I HLA and epitope-specific Ag-binding fragments, with experimentally determined interepitope and epitope to cell surface distances as constraints, revealed several sterically allowed and FRET-compatible class I HLA dimeric and tetrameric arrangements. Extension of the tetrameric class I HLA model with interacting TCR and CD8 resulted in a model of a supramolecular cluster that may exist physiologically and serve as a functionally significant unit for a network of CD8-HLA-I complexes providing enhanced signaling efficiency even at low MHC-peptide concentrations at the interface of effector and APCs.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Journal of immunology. - 166 : 8 (2001), p. 5078-5086. -
További szerzők:Bagossi Péter (1966-2011) (biokémikus, vegyész) Bene László (1963-) (biofizikus) Matkó János (1952-) (biológus) Szöllősi János (1953-) (biofizikus) Tőzsér József (1959-) (molekuláris biológus, biokémikus, vegyész) Fésüs László (1947-) (orvos biokémikus) Waldmann, Thomas A. Damjanovich Sándor (1936-2017) (biofizikus)
Pályázati támogatás:T029947
OTKA
F020590
OTKA
T019372
OTKA
T030399
OTKA
T023873
OTKA
T030411
OTKA
FKFP 327/2000
Egyéb
ETT T05/102/2000
Egyéb
FKFP 0518/99
Egyéb
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
DOI
Borító:

10.

001-es BibID:BIBFORM057538
035-os BibID:(scopus)84910122146 (wos)000345023400059
Első szerző:Govers, Coen
Cím:TCRs genetically linked to CD28 and CD3[epszilon] do not mispair with endogenous TCR chains and mediate enhanced t cell persistence and anti-melanoma activity / Coen Govers, Zsolt Sebestyén, János Roszik, Mandy van Brakel, Cor Berrevoets, Árpád Szöőr, Konstantina Panoutsopoulou, Marieke Broertjes, Tan Van, György Vereb, János Szöllősi, Reno Debets
Dátum:2014
ISSN:0022-1767 1550-6606
Megjegyzések:Adoptive transfer of T cells that are gene engineered to express a defined TCR represents a feasible and promising therapy for patients with tumors. However, TCR gene therapy is hindered by the transient presence and effectiveness of transferred T cells, which are anticipated to be improved by adequate T cell costimulation. In this article, we report the identification and characterization of a novel two-chain TCR linked to CD28 and CD3[epszilon] (i.e., TCR:28[epszilon]). This modified TCR demonstrates enhanced binding of peptide-MHC and mediates enhanced T cell function following stimulation with peptide compared with wild-type TCR. Surface expression of TCR:28[epszilon] depends on the transmembrane domain of CD28, whereas T cell functions depend on the intracellular domains of both CD28 and CD3[epszilon], with IL-2 production showing dependency on CD28:LCK binding. TCR:28[epszilon], but not wild-type TCR, induces detectable immune synapses in primary human T cells, and such immune synapses show significantly enhanced accumulation of TCR transgenes and markers of early TCR signaling, such as phosphorylated LCK and ERK. Importantly, TCR:28[epszilon] does not show signs of off-target recognition, as evidenced by lack of TCR mispairing, as well as preserved specificity. Notably, when testing TCR:28[epszilon] in immune-competent mice, we observed a drastic increase in T cell survival, which was accompanied by regression of large melanomas with limited recurrence. Our data argue that TCR transgenes that contain CD28, and, thereby, may provide T cell costimulation in an immune-suppressive environment, represent candidate receptors to treat patients with tumors.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
TCR
T Cell
Megjelenés:Journal Of Immunology. - 193 : 10 (2014), p. 5315-5326. -
További szerzők:Sebestyén Zsolt Roszik János (1979-) (biofizikus) van Brakel, Mandy Berrevoets, Cor Szöőr Árpád (1984-) (orvos) Panoutsopoulou, Konstantina Broertjes, Marieke Van, Tan Vereb György (1965-) (biofizikus, orvos) Szöllősi János (1953-) (biofizikus) Debets, Reno
Pályázati támogatás:TÁMOP-4.2.1/B-09/1/KONV-2010-0007
TÁMOP
TÁMOP-4.2.2/B-10/1/2010-0024
TÁMOP
TÁMOP-4.2.2/A-11/1/KONV-20120025
TÁMOP
OTKA-NK101337
OTKA
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

11.

001-es BibID:BIBFORM100193
035-os BibID:(Scopus)85123488729 (WOS)000745777900001
Első szerző:Guti Eliza (Molekuláris biológus)
Cím:The multitargeted receptor tyrosine kinase inhibitor sunitinib induces resistance of HER2 positive breast cancer cells to trastuzumab-mediated ADCC / Guti Eliza, Regdon Zsolt, Sturniolo Isotta, Kiss Alexandra, Kovács Katalin, Demény Máté, Szöőr Árpád, Vereb György, Szöllősi János, Hegedűs Csaba, Polgár Zsuzsanna, Virág László
Dátum:2022
ISSN:0340-7004
Megjegyzések:Despite recent advances in the development of novel personalized therapies, breast cancer continues to challenge physicians with resistance to various advanced therapies. The anticancer action of the anti-HER2 antibody, trastuzumab, involves antibody-dependent cell-mediated cytotoxicity (ADCC) by natural killer (NK) cells. Here, we report a repurposing screen of 774 clinically used compounds on NK-cell + trastuzumab-induced killing of JIMT-1 breast cancer cells. Using a calceinbased high-content screening (HCS) assay for the image-based quantitation of ADCC that we have developed and optimized for this purpose, we have found that the multitargeted tyrosine kinase inhibitor sunitinib inhibits ADCC in this model. The cytoprotective effect of sunitinib was also confirmed with two other assays (lactate dehydrogenase release, and electric cell substrate impedance sensing, ECIS). The drug suppressed NK cell activation as indicated by reduced granzyme B deposition on to the target cells and inhibition of interferon-? production by the NK cells. Moreover, sunitinib induced downregulation of HER2 on the target cells' surface, changed the morphology and increased adherence of the target cells. Moreover, sunitinib also triggered the autophagy pathway (speckled LC3b) as an additional potential underlying mechanism of the cytoprotective effect of the drug. Sunitinib-induced ADCC resistance has been confirmed in a 3D tumor model revealing the prevention of apoptotic cell death (Annexin V staining) in JIMT-1 spheroids co-incubated with NK cells and trastuzumab. In summary, our HCS assay may be suitable for the facile identification of ADCC boosting compounds. Our data urge caution concerning potential combinations of ADCC-based immunotherapies and sunitinib.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Sunitinib
Natural killer cell
Breast cancer
ADCC
Trastuzumab
Herceptin
Megjelenés:Cancer Immunology Immunotherapy. - 71 : 9 (2022), p. 2151-2168. -
További szerzők:Regdon Zsolt (1988-) (biokémikus, molekuláris biológus) Sturniolo, Isotta (1994-) Kiss Alexandra (1991-) (klinikai laboratóriumi kutató) Kovács Katalin (1978-) (biokémikus) Demény Máté Ágoston (1976-) (molekuláris biológus) Szöőr Árpád (1984-) (orvos) Vereb György (1965-) (biofizikus, orvos) Szöllősi János (1953-) (biofizikus) Hegedűs Csaba (1980-) (biokémikus, molekuláris biológus) Polgár Zsuzsanna (1978-) (agrármérnök, biotechnológus) Virág László (1965-) (biokémikus, sejtbiológus, farmakológus)
Pályázati támogatás:GINOP-2.3.3-15-2016-00020
GINOP
GINOP-2.3.2-15-2016-00048
GINOP
K132193
OTKA
K119690
OTKA
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

12.

001-es BibID:BIBFORM004665
035-os BibID:(scopus)0034033048 (wos)000086686100012
Első szerző:Hederer, Rosemarie A.
Cím:The CD45 tyrosine phosphatase regulates Campath-1H (CD52)-induced TCR-dependent signal transduction in human T cells / Hederer, R. A., Guntermann, C., Miller, N., Nagy, P., Szollosi, J., Damjanovich, S., Hale, G., Alexander, D. R.
Dátum:2000
Megjegyzések:Campath-1H, a humanized mAb undergoing clinical trials for treatment of leukemia, transplantation and autoimmune diseases, produces substantial lymphocyte depletion in vivo.The antibody binds to CD52, a highly glycosylated molecule attached to the membrane by a glycosylphosphatidylinositol anchor. Cross-linked Campath-1H is known to activate T cells in vitro. We have investigated the molecular basis for these effects by comparing the protein tyrosine phosphorylation signals induced by Campath-1H and the CD3 mAb OKT3 in primary T cells, and in CD45(+)TCR(+), CD45(-)TCR(+) and CD45(+)TCR(-) Jurkat subclones transfected with CD52. Our results show that Campath-1H triggers similar tyrosine phosphorylation events as OKT3 in both primary T cells and in the CD45(+)TCR(+) Jurkat sub-clone, albeit at quantitatively lower levels. However, no phospholipase C gamma 1 activation nor calcium signals were detected in response to CD52 ligation. The CD52-mediated induction of protein tyrosine phosphorylation was absolutely dependent upon the expression of both the TCR and the CD45 phosphotyrosine phosphatase at the cell surface. Cross-linking of Campath-1H was essential for signal transduction in all cells investigated. Fluorescence resonance energy transfer was used to demonstrate CD52 homo-association at the cell surface in Jurkat T cells in a TCR- and CD45-independent manner, and CD52-TCR association in CD45(+)TCR(+) cells. We propose a model to explain the activating effects of Campath-1H in which CD52 mAb cross-linking causes the trapping of TCR polypeptides within molecular complexes at the cell surface, thereby inducing signals via the TCR by a process which depends on the CD45-mediated regulation of the p56(lck) and p59(fyn) tyrosine kinases.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Antibodies, Monoclonal
Antibodies, Neoplasm
Antigens, CD
Antigens, CD45
Calcium
Calcium Signaling
Cells, Cultured
Comparative Study
Energy Transfer
enzymology
Fluorescence
genetics
Glycoproteins
Human
immunology
In Vitro
Inositol 1,4,5-Trisphosphate
Isoenzymes
Jurkat Cells
metabolism
Phospholipase C
physiology
Receptors, Antigen, T-Cell
Signal Transduction
Support, Non-U.S.Gov't
T-Lymphocytes
Transfection
Megjelenés:International Immunology. - 12 : 4 (2000), p. 505-516. -
További szerzők:Guntermann, Christine Miller, Nigel Nagy Péter (1971-) (biofizikus) Szöllősi János (1953-) (biofizikus) Damjanovich Sándor (1936-2017) (biofizikus) Hale, Geoffrey Alexander, Denis R.
Internet cím:DOI
elektronikus változat
Borító:
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