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@ARTICLE{Mertlitz:300093,
      author       = {S. Mertlitz$^*$ and K. Riesner$^*$ and M. Kalupa$^*$ and N.
                      Uhlig$^*$ and S. Cordes$^*$ and L. Verlaat$^*$ and M.
                      Jamali$^*$ and N. Li$^*$ and H. M. E. R. Mohamed$^*$ and L.
                      Bullinger$^*$ and S. Moss and J. Greenwood and J. Jatzlau
                      and P. Knaus and P. Vallecillo-Garcia$^*$ and O. Penack$^*$},
      title        = {{L}eucine-rich α-2 glycoprotein 1 ({LRG}1) during
                      inflammatory complications after allogeneic stem cell
                      transplantation and {CAR}-{T} cell therapy.},
      journal      = {Journal for ImmunoTherapy of Cancer},
      volume       = {13},
      number       = {3},
      issn         = {2051-1426},
      address      = {London},
      publisher    = {BioMed Central},
      reportid     = {DKFZ-2025-00593},
      pages        = {e009372},
      year         = {2025},
      abstract     = {Previous data indicated that the leucine-rich α-2
                      glycoprotein 1 (LRG1) pathway contributes to vascular
                      dysfunction during cancer growth. Therapeutic targeting of
                      LRG1 normalized tumor vessel dysfunction and enhanced the
                      efficacy of anti-cancer adoptive T cell therapy. A major
                      clinical problem after allogeneic hematopoietic stem cell
                      transplantation (alloHSCT) and after chimeric antigen
                      receptor (CAR) T-cell therapy is the induction of
                      hyperinflammatory side effects, which are typically
                      associated with severe endothelial dysfunction.We
                      investigated LRG1 in preclinical models and in patient
                      samples.In prospective studies, we found elevated LRG1 serum
                      levels in patients with cytokine release syndrome and immune
                      effector cell-associated neurotoxicity syndrome after
                      CAR-T-cell therapy as well as in patients with acute
                      graft-versus-host disease (aGVHD) after alloHSCT.In
                      preclinical models of aGVHD, we found vasculature-associated
                      LRG1 upregulation as well as LRG1 pathway gene upregulation.
                      The genetic deletion of LRG1 in alloHSCT donors and in
                      alloHSCT recipients led to reduced clinical and histological
                      aGVHD. In line with this, LRG1 deletion led to clinically
                      and histologically reduced disease severity in experimental
                      inflammatory models of colitis (dextran sulfate sodium
                      colitis) and paw edema. LRG1 deletion reduced
                      inflammation-related vascular leakiness, endothelial cell
                      proliferation, and migration.The current data support the
                      hypothesis that LRG1 is an attractive therapeutic target
                      after alloHSCT and after CAR-T cell therapy for cancer
                      because of its role in dysfunctional tumor vessels as well
                      as in inflammatory complications.},
      keywords     = {Humans / Animals / Glycoproteins: metabolism / Mice /
                      Immunotherapy, Adoptive: methods / Immunotherapy, Adoptive:
                      adverse effects / Graft vs Host Disease: etiology /
                      Hematopoietic Stem Cell Transplantation: adverse effects /
                      Hematopoietic Stem Cell Transplantation: methods / Male /
                      Transplantation, Homologous / Female / Inflammation / Middle
                      Aged / Cytokine Release Syndrome: etiology / Receptors,
                      Chimeric Antigen: metabolism / Prospective Studies /
                      Cytokine release syndrome (Other) / Graft versus host
                      disease - GVHD (Other) / Immune related adverse event - irAE
                      (Other) / Immunotherapy (Other) / Stem cell (Other) / LRG1
                      protein, human (NLM Chemicals) / Glycoproteins (NLM
                      Chemicals) / LRG1 protein, mouse (NLM Chemicals) /
                      Receptors, Chimeric Antigen (NLM Chemicals)},
      cin          = {BE01},
      ddc          = {610},
      cid          = {I:(DE-He78)BE01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40118496},
      doi          = {10.1136/jitc-2024-009372},
      url          = {https://inrepo02.dkfz.de/record/300093},
}