PuSH - Publikationsserver des Helmholtz Zentrums München: Targeting intracellular WT1 in AML with a novel RMF-peptide-MHC specific T-cell bispecific antibody.

Informationen

Hinweise zu Qualitätskriterien von Zeitschriften

Open-Access-Richtlinie der Helmholtz-Gemeinschaft 2016

CC Licencences

Metriken für Publikationen

Navigation

Startseite

English

EVA: Veröffentlichen

Neuer EVA Antrag

Recherche

Erweiterte Suche

Durchblättern nach ...

... HMGU-Autoren/Konsortien

... Organisationsstruktur

... Zeitschriften

... Publikationstypen

... Forschungsdaten

... Arbeitsgruppen

... Erscheinungsjahr

Publikationen im Überblick

Statistik

HGF Fortschrittsbericht

OA Publikationen

Eintragen

Neue Publikation eintragen

Neue Publikation holen aus...

...EVA

Fehlende Publikation melden

Highlights

Suche

Hilfe & Kontakt

Ansprechpartner

Hilfe

Datenschutz

Helmholtz Open Science

Bibliometrische Indikatoren

SHERPA/RoMEO

DOAJ

Export:

Text

Endnote (RIS) BIB

BibTeX

Augsberger, C.* ; Hänel, G.* ; Xu, W.* ; Pulko, V.* ; Hanisch, L.J.* ; Augustin, A.* ; Challier, J.* ; Hunt, K. ; Vick, B. ; Rovatti, P.E.* ; Krupka, C.* ; Rothe, M.* ; Schönle, A.* ; Sam, J.* ; Lezan, E.* ; Ducret, A.* ; Ortiz-Franyuti, D.* ; Walz, A.C.* ; Benz, J.* ; Bujotzek, A.* ; Lichtenegger, F.S.* ; Gassner, C.* ; Carpy, A.* ; Lyamichev, V.* ; Patel, J.* ; Konstandin, N.P.* ; Tunger, A.* ; Schmitz, M.* ; von Bergwelt-Baildon, M.* ; Spiekermann, K.* ; Vago, L.* ; Jeremias, I. ; Marrer-Berger, E.* ; Umaña, P.* ; Klein, C.* ; Subklewe, M.*

Targeting intracellular WT1 in AML with a novel RMF-peptide-MHC specific T-cell bispecific antibody.

Blood 138, 2655-2669 (2021)

Verlagsversion

DOI

PMC

	Closed

Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.

Abstract
Metriken
Zusatzinfos

Antibody-based immunotherapy is a promising strategy for targeting chemo-resistant leukemic cells. However, classical antibody-based approaches are restricted to targeting lineage-specific cell-surface antigens. By targeting intracellular antigens, a large number of other leukemia-associated targets would become accessible. In this study, we evaluated a novel T-cell bispecific (TCB) antibody, generated using CrossMab and knob-into-holes technology, containing a bivalent T-cell receptor-like binding domain that recognizes the RMFPNAPYL peptide derived from the intracellular tumor antigen Wilms' tumor 1 (WT1) in the context of human leukocyte antigen (HLA) A*02. Binding to CD3ε recruits T cells irrespective of their T-cell receptor specificity. WT1-TCB elicited antibody-mediated T-cell cytotoxicity against AML cell lines in a WT1- and HLA-restricted manner. Specific lysis of primary AML cells was mediated in ex vivo long-term co-cultures utilizing allogenic (mean specific lysis: 67±6% after 13-14 days; ±SEM; n=18) or autologous, patient-derived T cells (mean specific lysis: 54±12% after 11-14 days; ±SEM; n=8). WT1-TCB-treated T cells exhibited higher cytotoxicity against primary AML cells than an HLA-A*02 RMF-specific T-cell clone. Combining WT1-TCB with the immunomodulatory drug lenalidomide further enhanced antibody-mediated T-cell cytotoxicity against primary AML cells (mean specific lysis on day 3-4: 45.4±9.0% vs 70.8±8.3%; p=0.015; ±SEM; n=9-10). In vivo, WT1-TCB-treated humanized mice bearing SKM-1 tumors showed a significant and dose-dependent reduction in tumor growth. In summary, we show that WT1-TCB facilitates potent in vitro, ex vivo and in vivo killing of AML cell lines and primary AML cells; these results led to the initiation of a phase I trial in patients with r/r AML (NCT04580121).

Impact Factor

Scopus SNIP

Web of Science
Times Cited

Scopus
Cited By

Altmetric

22.113

0.000