All-trans retinoic acid enhances cytotoxic effect of T cells with an anti-CD38 chimeric antigen receptor in acute myeloid leukemia

Tetsumi Yoshida, Keichiro Mihara, Yoshifumi Takei, Kazuyoshi Yanagihara, Takanori Kubo, Joyeeta Bhattacharyya, Chihaya Imai, Tatsuji Mino, Yoshihiro Takihara, Tatsuo Ichinohe

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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 (499%), 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.

Original languageEnglish
Article numbere116
JournalClinical and Translational Immunology
Volume5
Issue number12
DOIs
Publication statusPublished - 01-12-2016

All Science Journal Classification (ASJC) codes

  • Nursing(all)
  • Immunology and Allergy
  • Immunology

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    Yoshida, T., Mihara, K., Takei, Y., Yanagihara, K., Kubo, T., Bhattacharyya, J., Imai, C., Mino, T., Takihara, Y., & Ichinohe, T. (2016). All-trans retinoic acid enhances cytotoxic effect of T cells with an anti-CD38 chimeric antigen receptor in acute myeloid leukemia. Clinical and Translational Immunology, 5(12), [e116]. https://doi.org/10.1038/cti.2016.73