% 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{Birocchi:180727,
      author       = {F. Birocchi and M. Cusimano and F. Rossari and S. Beretta
                      and P. M. V. Rancoita and A. Ranghetti and S. Colombo and B.
                      M. Costa$^*$ and P. Angel$^*$ and F. Sanvito and M. Callea
                      and R. Norata and L. Chaabane and T. Canu and A. Spinelli
                      and M. Genua and R. Ostuni and I. Merelli and N. Coltella
                      and L. Naldini},
      title        = {{T}argeted inducible delivery of immunoactivating cytokines
                      reprograms glioblastoma microenvironment and inhibits growth
                      in mouse models.},
      journal      = {Science translational medicine},
      volume       = {14},
      number       = {653},
      issn         = {1946-6234},
      address      = {Washington, DC},
      publisher    = {AAAS},
      reportid     = {DKFZ-2022-01518},
      pages        = {eabl4106},
      year         = {2022},
      note         = {DKFZ-ZMBH Alliance},
      abstract     = {Glioblastoma multiforme (GBM) is the most common and lethal
                      brain tumor characterized by a strongly immunosuppressive
                      tumor microenvironment (TME) that represents a barrier also
                      for the development of effective immunotherapies. The
                      possibility to revert this hostile TME by immunoactivating
                      cytokines is hampered by the severe toxicity associated with
                      their systemic administration. Here, we exploited a
                      lentiviral vector-based platform to engineer hematopoietic
                      stem cells ex vivo with the aim of releasing, via their
                      tumor-infiltrating monocyte/macrophage progeny,
                      interferon-α (IFN-α) or interleukin-12 (IL-12) at the
                      tumor site with spatial and temporal selectivity. Taking
                      advantage of a syngeneic GBM mouse model, we showed that
                      inducible release of IFN-α within the TME achieved robust
                      tumor inhibition up to eradication and outperformed systemic
                      treatment with the recombinant protein in terms of efficacy,
                      tolerability, and specificity. Single-cell RNA sequencing of
                      the tumor immune infiltrate revealed reprogramming of the
                      immune microenvironment toward a proinflammatory and
                      antitumoral state associated with loss of a macrophage
                      subpopulation shown to be associated with poor prognosis in
                      human GBM. The spatial and temporal control of IL-12 release
                      was critical to overcome an otherwise lethal hematopoietic
                      toxicity while allowing to fully exploit its antitumor
                      activity. Overall, our findings demonstrate a potential
                      therapeutic approach for GBM and set the bases for a
                      recently launched first-in-human clinical trial in patients
                      with GBM.},
      cin          = {A100},
      ddc          = {500},
      cid          = {I:(DE-He78)A100-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:35857642},
      doi          = {10.1126/scitranslmed.abl4106},
      url          = {https://inrepo02.dkfz.de/record/180727},
}