title: All-trans retinoic acid enhances cytotoxic effect of T cells with an anti-CD38 chimeric antigen receptor in acute myeloid leukemia.
abstract: We reported that T cells with anti-CD38-chimeric antigen receptors (CAR) eliminated B-cell lymphoma cells expressing CD38. To employ anti-CD38-CAR against acute myeloid leukemia (AML) blasts not expressing CD38, it is necessary to induce or increase the intensity of CD38 expression. A lactate dehydrogenase (LDH)-releasing assay and flow cytometry showed that anti-CD38-CAR T cells were cytotoxic against AML lines (THP-1 and CMK) expressing high CD38 levels (>99%), in time- and number of effector-dependent manners. In other AML lines (KG1, U937 and HL60) partially expressing CD38, CD38+AML cells were killed by CD38-specific T cells, but CD38-AML cells remained survived. Intriguingly, 10 nM all-trans retinoic acid (ATRA) augmented CD38 expression in KG1, U937 and HL60 cells and primary leukemic cells from AML patients. Moreover, the withdrawal of ATRA from the medium decreased CD38 expression in AML cells. Killing effects of anti-CD38-CAR T cells against AML lines and AML cells were limited without ATRA, whereas CD38-specific T cells enhanced cytotoxicity on AML cells by ATRA in association with enhanced CD38 expression. These results indicate that anti-CD38-CAR T cells eliminate AML cells through CD38 expression induced by ATRA.
authors.affiliation: Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University , Hiroshima, Japan.
authors.forename: Tetsumi
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University , Hiroshima, Japan.
authors.forename: Keichiro
authors.initials: K
authors.lastname: Mihara
authors.affiliation: Department of Biochemistry, Nagoya University Graduate School of Medicine , Nagoya, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Takei
authors.affiliation: Division of Translational Research, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center , Chiba, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Yanagihara
authors.affiliation: Department of Life Sciences, Yasuda Women's University Faculty of Pharmacy , Hiroshima, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Kubo
authors.affiliation: Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University , Hiroshima, Japan.
authors.forename: Joyeeta
authors.initials: J
authors.lastname: Bhattacharyya
authors.affiliation: Department of Pediatrics, Niigata University School of Medicine , Niigata, Japan.
authors.forename: Chihaya
authors.initials: C
authors.lastname: Imai
authors.affiliation: Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University , Hiroshima, Japan.
authors.forename: Tatsuji
authors.initials: T
authors.lastname: Mino
authors.affiliation: Department of Stem Cell Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University , Hiroshima, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Takihara
authors.affiliation: Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University , Hiroshima, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Ichinohe