Streptamer-based selection of WT1-specific CD8+ T cells for specific donor lymphocyte infusions

Experimental Hematology
Xinchao WangMichael Schmitt

Abstract

Donor lymphocyte infusions may generate a desirable graft-versus-leukemia effect, but also elicit a noxious graft-versus-host disease. A positive selection of leukemia (antigen)-specific T cells would be highly desirable. In this study, we focused on the immunogenic leukemia antigen Wilms' Tumor gene 1 (WT1). We employed the technology of streptamers available at good manufacturing practice level to first determine the frequency of human leukocyte antigen-A2 restricted WT1-specific CD8(+) T cells. Then, specific cells were labeled with streptamers and selected by magnetic cell separation. Purity and immunophenotype of selected cells were analyzed. Twenty-one of 40 healthy donors had naïve WT1-specific CD8(+) T-cell frequencies of >0.5%, and 8 of 40 even >1.0% of all CD8(+) T cells. In 7 of 10 acute myeloid leukemia patients, the frequencies were 0.5% to 3.65%. After positive selection by magnetic cell separation, a 60-fold increase with a purity of up to 17.79% in the lymphocyte gate and 86.18% in the CD8(+) T-cell gate could be achieved for CD8(+)WT1 streptamer(+)CD28(+/-)CD45RA(+)CCR7(-) effector T cells. Streptamer technology allows selection of pure WT1-specific effector T cells. This is a prerequisite for clinical applicat...Continue Reading

Citations

Oct 1, 2013·Cellular and Molecular Life Sciences : CMLS·Natalia RamírezEduardo Olavarría
Jul 12, 2013·Leukemia & Lymphoma·Nan JinMichael Schmitt
Nov 1, 2015·International Journal of Cancer. Journal International Du Cancer·Rosaely Casalegno-GarduñoMichael Schmitt
Oct 16, 2014·Journal for Immunotherapy of Cancer·Seth M PollackCassian Yee
Sep 20, 2011·Best Practice & Research. Clinical Haematology·Shigeo FujiHermann Einsele
May 26, 2017·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Sarah MatkoMarcus Odendahl
Jul 21, 2017·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Ulrich Sack
Aug 9, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Willem J J FalkenburgInge Jedema
May 14, 2021·Blood·Christoph Schmid

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