% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Teibo:303211,
      author       = {J. O. Teibo and R. M. Silveira and V. C. Silvestrini and I.
                      Archiolli and A. PaulaMasson and B. P. de Morais and D.
                      Schmidt and M. H. Dos Santos and G. A. Ferreira and C. H.
                      Thomé and D. Helm$^*$ and R. S. Nirujogi and D. R. Alessi
                      and V. Picanço-Castro and L. E. B. de Souza and V. M.
                      Faça},
      title        = {{P}roteomics analysis reveals early event molecular
                      effectors of anti-{CD}19 {CAR}-{T} cell therapy in
                      hematological cancer.},
      journal      = {Journal of proteomics},
      volume       = {321},
      issn         = {1874-3919},
      address      = {New York, NY [u.a.]},
      publisher    = {Elsevier},
      reportid     = {DKFZ-2025-01562},
      pages        = {105507},
      year         = {2025},
      note         = {Volume 321, 30 October 2025, 105507Journal of Proteomics},
      abstract     = {Chimeric antigen receptor T-cell (CAR-T) therapy is at the
                      forefront of the field of cell immunotherapy. In this study,
                      we generated an anti-CD19 CAR-Jurkat T cell line using a
                      locally produced second-generation anti-CD19 CAR construct,
                      which allowed us to analyse early proteomic changes that are
                      crucial for comprehending the signalling pathways and
                      mechanism of action of this CAR-T cell. SILAC-heavy tagged
                      RAJI B-cells and anti-CD19 CAR-Jurkat T-cells were
                      co-cultured for ten minutes. The proteomic profiles were
                      acquired via DIA methodology on the Orbitrap Astral LC-MS/MS
                      platform. The proteome was extensively covered, resulting in
                      about 8800 protein identifications at 1 $\%$ FDR. The
                      effector CAR-Jurkat cells showed proteomic changes involving
                      antigen presentation by CD74. The target RAJI B-cells
                      exhibited more significant alterations. Effector proteins,
                      namely CD247, CD28, DAP, LCK, p38 MAPK, and CASP3, were
                      validated, as they have critical roles in antigen
                      presentation, T-cell activation, and apoptosis.
                      Pharmacological inhibition of LCK using Dasatinib further
                      suggested its pivotal role in early CAR-T signalling. This
                      study led us to identify proteins that function as molecular
                      effectors of anti-CD19 CAR-T cell therapy during the initial
                      phases of CAR-T-target cell engagement, advancing our
                      knowledge of the mechanism and signalling pathways that will
                      support CAR-T cell development. SIGNIFICANCE: Chimeric
                      antigen receptor T-cell (CAR-T cell) therapy is
                      state-of-the-art in cell and immunotherapy. Determining
                      important players in cellular communication and signalling
                      mediated by membranes and intracellular proteins require
                      understanding the connection between tumours and modified
                      cells. We employed global proteomics in this study to better
                      grasp the functional protein networks using a
                      high-sensitivity mass spectrometric platform for protein
                      identification and quantification. We identified proteins as
                      molecular effectors of anti-CD19 CAR-T cell treatment during
                      the early stages of CAR-T-target cell interaction. Our
                      understanding of the mechanism and signalling pathways will
                      promote the development of new CAR constructs and improve
                      the efficacy and ability to overcome the resistance of this
                      innovative cancer treatment strategy, which will advance the
                      identification of adjuvant molecules for the regulation of
                      CAR-T responses.},
      keywords     = {CAR-T cell (Other) / Early Signalling event (Other) /
                      Hematological Cancer (Other) / Molecular effectors (Other) /
                      Proteomics (Other) / SILAC (Other)},
      cin          = {W120},
      ddc          = {540},
      cid          = {I:(DE-He78)W120-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40716489},
      doi          = {10.1016/j.jprot.2025.105507},
      url          = {https://inrepo02.dkfz.de/record/303211},
}