• Medientyp: E-Artikel
  • Titel: Systemic treatment with CAR-engineered T cells against PSCA delays subcutaneous tumor growth and prolongs survival of mice
  • Beteiligte: Hillerdal, Victoria; Ramachandran, Mohanraj; Leja, Justyna; Essand, Magnus
  • Erschienen: Springer Science and Business Media LLC, 2014
  • Erschienen in: BMC Cancer
  • Sprache: Englisch
  • DOI: 10.1186/1471-2407-14-30
  • ISSN: 1471-2407
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Adoptive transfer of T cells genetically engineered with a chimeric antigen receptor (CAR) has successfully been used to treat both chronic and acute lymphocytic leukemia as well as other hematological cancers. Experimental therapy with CAR-engineered T cells has also shown promising results on solid tumors. The prostate stem cell antigen (PSCA) is a protein expressed on the surface of prostate epithelial cells as well as in primary and metastatic prostate cancer cells and therefore a promising target for immunotherapy of prostate cancer.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>We developed a third-generation CAR against PSCA including the CD28, OX-40 and CD3 ζ signaling domains. T cells were transduced with a lentivirus encoding the PSCA-CAR and evaluated for cytokine production (paired Student’s t-test), proliferation (paired Student’s t-test), CD107a expression (paired Student’s t-test) and target cell killing <jats:italic>in vitro</jats:italic> and tumor growth and survival <jats:italic>in vivo</jats:italic> (Log-rank test comparing Kaplan-Meier survival curves).</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>PSCA-CAR T cells exhibit specific interferon (IFN)-γ and interleukin (IL)-2 secretion and specific proliferation in response to PSCA-expressing target cells. Furthermore, the PSCA-CAR-engineered T cells efficiently kill PSCA-expressing tumor cells <jats:italic>in vitro</jats:italic> and systemic treatment with PSCA-CAR-engineered T cells significantly delays subcutaneous tumor growth and prolongs survival of mice.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Our data confirms that PSCA-CAR T cells may be developed for treatment of prostate cancer.</jats:p> </jats:sec>
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