Activated T-cell-mediated immunotherapy with a chimeric receptor against CD38 in b-cell non-hodgkin lymphoma

Keichiro Mihara, Kazuyoshi Yanagihara, Misato Takigahira, Chihaya Imai, Akira Kitanaka, Yoshihiro Takihara, Akiro Kimura

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

Abstract

T-cell-mediated immunotherapy with a chimeric antigen receptor (CAR) is expected to become a powerful treatment for cancer. CD38, highly expressed in B-cell non-Hodgkin lymphoma (B-NHL) cells, is an attractive target in immunotherapy for B-NHL. We retrovirally transduced a T-cell line, Hut78, expressing little CD38, with an anti-CD38-CAR. Hut78 cells with the anti-CD38-CAR were cocultured with B-NHL cell lines bearing CD38 and also B-NHL cells from patients. Four days later most of the lymphoma cells were killed (the level of cytotoxicity was >95%). By contrast, there was undetectable cytotoxicity against CD38-negative cell lines. Then, we introduced the anti-CD38-CAR into human peripheral T cells. However, the recovery of viable cells was very low, presumably because of an autolytic reaction caused by the association of the anti-CD38-CAR with CD38 on the cell surface. The addition of an anti-CD38 antibody increased the yield of viable transduced T cell probably by blocking the autolytic reaction. We cocultured human peripheral T cells bearing anti-CD38-CAR with B-NHL cells. The median specific cytotoxicity was greater than 90%. These cells were injected 4 times into NOD/SCID mice, which were inoculated with B-NHL cells luciferase. Luciferase activity was not detectable even 30 days after the inoculation in 5 of 6 mice injected. By contrast, it increased in all of the mice injected with the mock vector-transduced T cell. In conclusion, T cell with the anti-CD38-CAR showed powerful cytotoxicity against B-NHL cells in vitro and in vivo. These findings may provide an important clue for improving the methodology of T-cell-mediated immunotherapy

Original languageEnglish
Pages (from-to)737-743
Number of pages7
JournalJournal of Immunotherapy
Volume32
Issue number7
DOIs
Publication statusPublished - 09-2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

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