Antitumor activity of CAR-T cells targeting the intracellular oncoprotein WT1 can be enhanced by vaccination

Yasushi Akahori, Linan Wang, Motohiro Yoneyama, Naohiro Seo, Satoshi Okumura, Yoshihiro Miyahara, Yasunori Amaishi, Sachiko Okamoto, Junichi Mineno, Hiroaki Ikeda, Takehiro Maki, Hiroshi Fujiwara, Yoshiki Akatsuka, Takuma Kato, Hiroshi Shiku

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

The recent success of chimeric antigen receptor (CAR)-T cell therapy for treatment of hematologic malignancies supports further development of treatments for both liquid and solid tumors. However, expansion of CAR-T cell therapy is limited by the availability of surface antigens specific for the tumor while sparing normal cells. There is a rich diversity of tumor antigens from intracellularly expressed proteins that current and conventional CAR-T cells are unable to target. Furthermore, adoptively transferred T cells often suffer from exhaustion and insufficient expansion, in part, because of the immunosuppressive mechanisms operating in tumor-bearing hosts. Therefore, it is necessary to develop means to further activate and expand those CAR-T cells in vivo. The Wilms tumor 1 (WT1) is an intracellular oncogenic transcription factor that is an attractive target for cancer immunotherapy because of its overexpression in a wide range of leukemias and solid tumors, and a low level of expression in normal adult tissues. In the present study, we developed CART cells consisting of a single chain variable fragment (scFv) specific to the WT1235-243/HLA-A*2402 complex. The therapeutic efficacy of our CAR-T cells was demonstrated in a complex can be boosted by vaccination.

Original languageEnglish
Pages (from-to)1134-1145
Number of pages12
JournalBlood
Volume132
Issue number11
DOIs
Publication statusPublished - 13-09-2018

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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