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Enhanced stimulation of antigen-specific immune responses against nucleophosmin 1 mutated acute myeloid leukaemia by an anti-programmed death 1 antibody

Greiner, Jochen; Goetz, Marlies; Schuler, Patrick J.; Bulach, Christiane; Hofmann, Susanne; Schrezenmeier, Hubert; D?hner, Harmut; Schneider, Vanessa; Guinn, Barbara ann

Authors

Jochen Greiner

Marlies Goetz

Patrick J. Schuler

Christiane Bulach

Susanne Hofmann

Hubert Schrezenmeier

Harmut D?hner

Vanessa Schneider



Abstract

Nucleophosmin1 (NPM1) is one of the most commonly mutated genes in AML and is often associated with a favourable prognosis. Immune responses play an increasing role in AML treatment decisions; however, the role of immune checkpoint inhibition is still not clear. To address this, we investigated specific immune responses against NPM1, and three other leukaemia-associated antigens (LAA), PRAME, Wilms' tumour 1 and RHAMM in AML patients. We investigated T cell responses against leukaemic progenitor/stem cells (LPC/LSC) using colony-forming immunoassays and flow cytometry. We examined whether immune checkpoint inhibition with the anti-programmed death 1 antibody increases the immune response against stem cell-like cells, comparing cells from NPM1 mutated and NPM1 wild-type AML patients. We found that the anti-PD-1 antibody, nivolumab, increases LAA stimulated cytotoxic T lymphocytes and the cytotoxic effect against LPC/LSC. The effect was strongest against NPM1mut cells when the immunogenic epitope was derived from the mutated region of NPM1 and these effects were enhanced through the addition of anti-PD-1. The data suggest that patients with NPM1 mutated AML could be treated with the immune checkpoint inhibitor anti-PD-1 and that this treatment combined with NPM1-mutation specific directed immunotherapy could be even more effective for this unique group of patients.

Citation

Greiner, J., Goetz, M., Schuler, P. J., Bulach, C., Hofmann, S., Schrezenmeier, H., …Guinn, B. A. (2022). Enhanced stimulation of antigen-specific immune responses against nucleophosmin 1 mutated acute myeloid leukaemia by an anti-programmed death 1 antibody. British journal of haematology, 198(5), 866-874. https://doi.org/10.1111/bjh.18326

Journal Article Type Article
Acceptance Date Jun 10, 2022
Online Publication Date Jul 7, 2022
Publication Date 2022-09
Deposit Date Jun 26, 2022
Publicly Available Date Oct 27, 2022
Journal British Journal of Haematology
Print ISSN 0007-1048
Electronic ISSN 1365-2141
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 198
Issue 5
Pages 866-874
DOI https://doi.org/10.1111/bjh.18326
Keywords Acute myeloid leukaemia; Nucleophosmin 1; NPM1 mutation; Anti-PD-1
Public URL https://hull-repository.worktribe.com/output/4014249

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Publisher Licence URL
http://creativecommons.org/licenses/by-nc/4.0

Copyright Statement
© 2022 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.







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