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@ARTICLE{Das:144790,
      author       = {K. Das$^*$ and D. Eisel$^*$ and M. Vormehr and K.
                      Müller-Decker$^*$ and A. Hommertgen$^*$ and D. Jäger$^*$
                      and I. Zörnig and M. Feuerer and A. Kopp-Schneider$^*$ and
                      W. Osen$^*$ and S. Eichmüller$^*$},
      title        = {{A} transplantable tumor model allowing investigation of
                      {NY}-{BR}-1-specific {T} cell responses in {HLA}-{DRB}1*0401
                      transgenic mice.},
      journal      = {BMC cancer},
      volume       = {19},
      number       = {1},
      issn         = {1471-2407},
      address      = {Heidelberg},
      publisher    = {Springer},
      reportid     = {DKFZ-2019-02222},
      pages        = {914},
      year         = {2019},
      abstract     = {NY-BR-1 has been described as a breast cancer associated
                      differentiation antigen with intrinsic immunogenicity giving
                      rise to endogenous T and B cell responses. The current study
                      presents the first murine tumor model allowing functional
                      investigation of NY-BR-1-specific immune responses in vivo.A
                      NY-BR-1 expressing tumor model was established in DR4tg mice
                      based on heterotopic transplantation of stable transfectant
                      clones derived from the murine H2 compatible breast cancer
                      cell line EO771. Composition and phenotype of tumor
                      infiltrating immune cells were analyzed by qPCR and FACS.
                      MHC I binding affinity of candidate CTL epitopes predicted
                      in silico was determined by FACS using the mutant cell line
                      RMA-S. Frequencies of NY-BR-1 specific CTLs among
                      splenocytes of immunized mice were quantified by FACS with
                      an epitope loaded Db-dextramer. Functional CTL activity was
                      determined by IFNγ catch or IFNγ ELISpot assays and
                      statistical analysis was done applying the Mann Whitney
                      test. Tumor protection experiments were performed by
                      immunization of DR4tg mice with replication deficient
                      recombinant adenovirus followed by s.c. challenge with
                      NY-BR-1 expressing breast cancer cells.Our results show
                      spontaneous accumulation of CD8+ T cells and F4/80+ myeloid
                      cells preferentially in NY-BR-1 expressing tumors. Upon
                      NY-BR-1-specific immunization experiments combined with in
                      silico prediction and in vitro binding assays, the first
                      NY-BR-1-specific H2-Db-restricted T cell epitope could be
                      identified. Consequently, flow cytometric analysis with
                      fluorochrome conjugated multimers showed enhanced
                      frequencies of CD8+ T cells specific for the newly
                      identified epitope in spleens of immunized mice. Moreover,
                      immunization with Ad.NY-BR-1 resulted in partial protection
                      against outgrowth of NY-BR-1 expressing tumors and promoted
                      intratumoral accumulation of macrophages.This study
                      introduces the first H2-Db-resctricted CD8+ T cell
                      epitope-specific for the human breast cancer associated
                      tumor antigen NY-BR-1. Our novel, partially humanized tumor
                      model enables investigation of the interplay between
                      HLA-DR4-restricted T cell responses and CTLs within their
                      joint attack of NY-BR-1 expressing tumors.},
      cin          = {D210 / W420 / D120 / C060},
      ddc          = {610},
      cid          = {I:(DE-He78)D210-20160331 / I:(DE-He78)W420-20160331 /
                      I:(DE-He78)D120-20160331 / I:(DE-He78)C060-20160331},
      pnm          = {314 - Tumor immunology (POF3-314)},
      pid          = {G:(DE-HGF)POF3-314},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:31519152},
      doi          = {10.1186/s12885-019-6102-6},
      url          = {https://inrepo02.dkfz.de/record/144790},
}