TY - JOUR
T1 - In vitro and in vivo antitumor effect of anti-CD33 chimeric receptor-expressing EBV-CTL against CD 33 + acute myeloid leukemia
AU - Dutour, A.
AU - Marin, V.
AU - Pizzitola, I.
AU - Valsesia-Wittmann, S.
AU - Lee, D.
AU - Yvon, E.
AU - Finney, H.
AU - Lawson, A.
AU - Brenner, M.
AU - Biondi, A.
AU - Biagi, E.
AU - Rousseau, R.
PY - 2012
Y1 - 2012
N2 - Genetic engineering of T cells with chimeric T-cell receptors (CARs) is an attractive strategy to treat malignancies. It extends the range of antigens for adoptive T-cell immunotherapy, and major mechanisms of tumor escape are bypassed. With this strategy we redirected immune responses towards the CD33 antigen to target acute myeloid leukemia. To improve in vivo T-cell persistence, we modified human Epstein Barr Virus-(EBV-) specific cytotoxic T cells with an anti-CD33.CAR. Genetically modified T cells displayed EBV and HLA-unrestricted CD33 bispecificity in vitro. In addition, though showing a myeloablative activity, they did not irreversibly impair the clonogenic potential of normal CD34+ hematopoietic progenitors. Moreover, after intravenous administration into CD33+ human acute myeloid leukemia-bearing NOD-SCID mice, anti-CD33-EBV- specific T cells reached the tumor sites exerting antitumor activity in vivo. In conclusion, targeting CD33 by CAR-modified EBV-specific T cells may provide additional therapeutic benefit to AML patients as compared to conventional chemotherapy or transplantation regimens alone.
AB - Genetic engineering of T cells with chimeric T-cell receptors (CARs) is an attractive strategy to treat malignancies. It extends the range of antigens for adoptive T-cell immunotherapy, and major mechanisms of tumor escape are bypassed. With this strategy we redirected immune responses towards the CD33 antigen to target acute myeloid leukemia. To improve in vivo T-cell persistence, we modified human Epstein Barr Virus-(EBV-) specific cytotoxic T cells with an anti-CD33.CAR. Genetically modified T cells displayed EBV and HLA-unrestricted CD33 bispecificity in vitro. In addition, though showing a myeloablative activity, they did not irreversibly impair the clonogenic potential of normal CD34+ hematopoietic progenitors. Moreover, after intravenous administration into CD33+ human acute myeloid leukemia-bearing NOD-SCID mice, anti-CD33-EBV- specific T cells reached the tumor sites exerting antitumor activity in vivo. In conclusion, targeting CD33 by CAR-modified EBV-specific T cells may provide additional therapeutic benefit to AML patients as compared to conventional chemotherapy or transplantation regimens alone.
UR - http://www.scopus.com/inward/record.url?scp=84863019415&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84863019415&partnerID=8YFLogxK
U2 - 10.1155/2012/683065
DO - 10.1155/2012/683065
M3 - Article
C2 - 22272203
AN - SCOPUS:84863019415
VL - 2012
JO - Advances in Hematology
JF - Advances in Hematology
SN - 1687-9104
M1 - 683065
ER -