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Potential role of adoptively transferred allogeneic WT1-specific CD4+ and CD8+ T lymphocytes for the sustained remission of refractory AML

Bone Marrow Transplantation volume 45, pages 597–599 (2010)Cite this article

Donor lymphocyte infusion (DLI) has shown limited clinical benefit in a minority of patients with relapsed AML after transplant.1 Adoptive transfer of in vitro generated leukemia-specific cytotoxic T lymphocytes (CTLs), instead of non-manipulated DLI, may have the advantages of both circumventing inadequate antigen presentation and inducing leukemia-specific immune reaction.2, 3 Wilms’ tumor gene 1 (WT1) is considered a promising target for leukemia,4, 5 but the feasibility of the therapeutic use of WT1-specific CTL has not been reported yet.

For in vitro generation of WT1-CTLs, we made recombinant adenovirus encoding truncated WT1 (Adv-ΔWT1), which was created by the deletion of the N-terminus (1–147aa) of full-length WT1. Immature DCs induced from donor CD14+ monocytes were infected with Adv-ΔWT1, matured and cocultivated with donor lymphocytes.6 After three rounds of stimulation, CTLs were cryopreserved for later usage and some remaining cells were analyzed. The proportions of CD4+ cells and CD8+ T cells were 30% and 66% and most of the CD8+ T cells were effector memory cells (CCR7−CD45RA−). CTLs showed specific cytotoxicity against autologous LCL transfected with ΔWT1-encoding RNA. ELISPOT assay showed high frequencies of ΔWT1-specific IFN-γ-secreting T cells in both CD4+ and CD8+ T cells. IFN-γ-secreting T cells specific for WT1–187 and WT1–235 peptides located within ΔWT1 were detected in higher frequencies compared with those for unlocated WT1–126.

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Acknowledgements

This study was supported by a grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (A040018). This work was also supported by the Catholic Medical Center, Institute of Cell therapy research Grant funded by the Committee for Life in the Archdiocese of Seoul.

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Authors and Affiliations

  1. Catholic Blood and Marrow Transplantation Center, Seoul St Mary's Hospital, Seoul, Republic of Korea

    Y-J Kim, S-G Cho, S Lee, B-S Cho, K-S Eom, C-K Min, H-J Kim, D-W Kim, J-W Lee, W-S Min & C-C Kim

  2. Catholic Hematopoietic Stem Cell Bank,

    E-K Kim, H-J Sohn, H B Choi & T-G Kim

  3. Department of Diagnostic Laboratory, Seoul St Mary's Hospital, Seoul, Republic of Korea

    M-S Kim & Y-G Kim

  4. Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

    T-G Kim

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Correspondence to T-G Kim.

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Kim, YJ., Cho, SG., Lee, S. et al. Potential role of adoptively transferred allogeneic WT1-specific CD4+ and CD8+ T lymphocytes for the sustained remission of refractory AML. Bone Marrow Transplant 45, 597–599 (2010). https://doi.org/10.1038/bmt.2009.191

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