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@ARTICLE{Brinkmann:290535,
author = {B. J. Brinkmann and A. Floerchinger and C. Schniederjohann
and T. Roider and M. Coelho and N. Mack$^*$ and P.-M. Bruch
and N. Liebers and S. Dötsch and D. H. Busch and M.
Schmitt$^*$ and F. Neumann and P. M. Roessner$^*$ and M.
Seiffert$^*$ and S. Dietrich},
title = {{CD}20-bispecific antibodies improve response to
{CD}19-{CAR} {T}-cells in lymphoma in-vitro and {CLL}
in-vivo models.},
journal = {Blood},
volume = {144},
number = {7},
issn = {0006-4971},
address = {Washington, DC},
publisher = {American Society of Hematology},
reportid = {DKFZ-2024-01152},
pages = {784-789},
year = {2024},
note = {2024 Aug 15;144(7):784-789},
abstract = {Anti-CD19 chimeric antigen receptor T-cells (CD19-CAR)
represent an effective treatment for relapsed/refractory
B-cell malignancies but incomplete responses often result in
early disease progression. We here assessed potential
benefits of co-administering CD20-targeting bispecific
antibodies (CD20-BsAb) with CD19-CAR, aiming to enhance
immunotherapeutic efficacy. Addition of CD20-BsAb to
co-cultures of CD19-CAR and primary samples of B-cell
malignancies, comprising malignant B- and endogenous
T-cells, significantly improved killing of malignant cells
alongside enhanced expansion of both endogenous T-cells and
CD19-CAR. CD20-BsAb induced an increase in proliferation and
activation of endogenous T-cells and CD19-CAR. In an
immunocompetent mouse model of CLL, relapse after initial
treatment response frequently occurred after CD19-CAR
monotherapy. Combination with injections of CD20-BsAb
significantly enhanced treatment response and resulted in
improved eradication of malignant cells. Higher efficacy was
accompanied by improved T-cell expansion upon CD20-BsAb
administration and resulted in longer survival, with $80\%$
of mice being cured with no detectable malignant cell
population within eight weeks of therapy initiation.
Collectively, our in-vitro and in-vivo data demonstrate
enhanced therapeutic efficacy of CD19-CAR when combined with
CD20-BsAb in B-cell malignancies. Activation and
proliferation of both infused CAR T-cells as well as
endogenous T-cells may contribute to improved disease
control.},
cin = {B062 / B060 / HD01},
ddc = {610},
cid = {I:(DE-He78)B062-20160331 / I:(DE-He78)B060-20160331 /
I:(DE-He78)HD01-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:38805637},
doi = {10.1182/blood.2023022682},
url = {https://inrepo02.dkfz.de/record/290535},
}