Home > Publications database > CD20-bispecific antibodies improve response to CD19-CAR T-cells in lymphoma in-vitro and CLL in-vivo models. > print

001     290535
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100 1 _ |a Brinkmann, Berit J
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245 _ _ |a CD20-bispecific antibodies improve response to CD19-CAR T-cells in lymphoma in-vitro and CLL in-vivo models.
260 _ _ |a Washington, DC
|c 2024
|b American Society of Hematology
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500 _ _ |a 2024 Aug 15;144(7):784-789
520 _ _ |a 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.
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700 1 _ |a Floerchinger, Alessia
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700 1 _ |a Schniederjohann, Christina
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700 1 _ |a Roider, Tobias
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700 1 _ |a Coelho, Mariana
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700 1 _ |a Mack, Norman
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700 1 _ |a Bruch, Peter-Martin
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700 1 _ |a Liebers, Nora
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700 1 _ |a Dötsch, Sarah
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700 1 _ |a Busch, Dirk H
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700 1 _ |a Schmitt, Michael
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700 1 _ |a Neumann, Frank
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700 1 _ |a Roessner, Philipp M
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700 1 _ |a Seiffert, Martina
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700 1 _ |a Dietrich, Sascha
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