Research output: Contribution to journal › Article › peer-review
VEGFR2-specific FnCAR effectively redirects the cytotoxic activity of T cells and YT NK cells. / Kulemzin, Sergey V.; Gorchakov, Andrey A.; Chikaev, Anton N. et al.
In: Oncotarget, Vol. 9, No. 10, 06.02.2018, p. 9021-9029.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - VEGFR2-specific FnCAR effectively redirects the cytotoxic activity of T cells and YT NK cells
AU - Kulemzin, Sergey V.
AU - Gorchakov, Andrey A.
AU - Chikaev, Anton N.
AU - Kuznetsova, Valeriya V.
AU - Volkova, Olga Y.
AU - Matvienko, Daria A.
AU - Petukhov, Alexey V.
AU - Zaritskey, Andrey Y.
AU - Taranin, Alexandr V.
PY - 2018/2/6
Y1 - 2018/2/6
N2 - T and NK cells armed with chimeric antigen receptors (CAR) are promising tools for the specific elimination of cancer cells. In most CAR designs implemented to date, the recognition of target cells is mediated by single-chain variable fragments (scFvs) derived from murine monoclonal antibodies. This format, however, has a number of limitations, including its relatively large size and potential immunogenicity in humans. In this study, we explored the feasibility of using human fibronectin type III domains (Fn3) as the antigen recognition domain in CARs. Human Fn3 domains have lower predicted immunogenicity compared to mouse-derived sequences, and a reduced molecular weight compared to scFvs. We created a functional CAR using a VEGFR2- specific Fn3 module replacing the conventional scFv. The resulting FnCAR specifically potentiates the cytotoxic activity of human T cells and YT NK cells in the presence of VEGFR2-positive targets. These findings demonstrate that Fn3 domains can be used in CARs for antigen recognition.
AB - T and NK cells armed with chimeric antigen receptors (CAR) are promising tools for the specific elimination of cancer cells. In most CAR designs implemented to date, the recognition of target cells is mediated by single-chain variable fragments (scFvs) derived from murine monoclonal antibodies. This format, however, has a number of limitations, including its relatively large size and potential immunogenicity in humans. In this study, we explored the feasibility of using human fibronectin type III domains (Fn3) as the antigen recognition domain in CARs. Human Fn3 domains have lower predicted immunogenicity compared to mouse-derived sequences, and a reduced molecular weight compared to scFvs. We created a functional CAR using a VEGFR2- specific Fn3 module replacing the conventional scFv. The resulting FnCAR specifically potentiates the cytotoxic activity of human T cells and YT NK cells in the presence of VEGFR2-positive targets. These findings demonstrate that Fn3 domains can be used in CARs for antigen recognition.
KW - Chimeric antigen receptors
KW - Fn3
KW - FnCAR
KW - NK cells
KW - VEGFR2
UR - http://www.scopus.com/inward/record.url?scp=85041402527&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.24078
DO - 10.18632/oncotarget.24078
M3 - Article
C2 - 29507671
AN - SCOPUS:85041402527
VL - 9
SP - 9021
EP - 9029
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 10
ER -
ID: 12099862