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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>