% 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{AbuAhmad:303114,
      author       = {M. Abu Ahmad and O. Radinsky and B. Kaufman and K. Waidha
                      and E. Gharra and S. Dim and D. B. Manikandan and N. Ofir
                      and D. Jäger$^*$ and M. Meyer$^*$ and M. Elkabets and K. S.
                      Campbell and M. Zektser and R. Gazit and O. Rouvio and F.
                      Momburg$^*$ and A. Porgador},
      title        = {{HLA}-{E}[p{HLA}-{G}] {C}omplex {S}pecific {M}onoclonal
                      {A}ntibody {E}nhancing {NK} {A}ctivity in {M}ultiple
                      {M}yeloma.},
      journal      = {Blood advances},
      volume       = {nn},
      issn         = {2473-9529},
      address      = {Washington, DC},
      publisher    = {American Society of Hematology},
      reportid     = {DKFZ-2025-01533},
      pages        = {nn},
      year         = {2025},
      note         = {epub},
      abstract     = {HLA-E presenting the HLA-G leader peptide VMAPRTLFL
                      (HLA-E[pHLA-G]) on tumor cells plays a crucial role in
                      suppressing natural killer(NK) and cytotoxic CD8+ T cells
                      through NKG2A interaction. While blocking HLA-E:NKG2A is a
                      promising immune checkpoint(IC) approach in cancer therapy,
                      toxicity remains a major clinical concern. We developed a
                      novel immune checkpoint inhibitor(ICI) that selectively
                      prevents HLA-E:NKG2A interaction, a monoclonal antibody(mAb)
                      that selectively targets the HLA-E[pHLA-G] complex,
                      distinguishing cancerous from non-cancerous cells. In
                      clinical bone marrow samples from multiple myeloma(MM)
                      patients, 4D7 specifically recognized tumor-associated
                      HLA-E-peptide complexes. Using NK cells from healthy donors,
                      4D7 effectively blocked the HLA-E:NKG2A interaction and
                      enhanced NKG2A-positive NK cell activity in autologous MM
                      cell co-cultures. Importantly, 4D7 did not inhibit
                      NKG2C-positive NK cells, preserving their activity. Even
                      though NKG2C also interacts with HLA-E. In MM-bearing mice
                      treated with human NK cells, 4D7 significantly reduced tumor
                      growth. This targeted approach activates NK cells only
                      against tumor cells presenting HLA-E-peptide complexes,
                      potentially minimizing toxicity compared to current NKG2A
                      inhibitors. The development of 4D7 highlights a promising
                      advancement in immunotherapy for hematological malignancies,
                      offering improved outcomes for MM patients and a foundation
                      for broader application across cancer types.},
      cin          = {D120},
      ddc          = {610},
      cid          = {I:(DE-He78)D120-20160331},
      pnm          = {314 - Immunologie und Krebs (POF4-314)},
      pid          = {G:(DE-HGF)POF4-314},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40706037},
      doi          = {10.1182/bloodadvances.2025016276},
      url          = {https://inrepo02.dkfz.de/record/303114},
}