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000290535 1001_ $$aBrinkmann, Berit J$$b0
000290535 245__ $$aCD20-bispecific antibodies improve response to CD19-CAR T-cells in lymphoma in-vitro and CLL in-vivo models.
000290535 260__ $$aWashington, DC$$bAmerican Society of Hematology$$c2024
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000290535 500__ $$a2024 Aug 15;144(7):784-789
000290535 520__ $$aAnti-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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000290535 7001_ $$00009-0004-5452-9417$$aFloerchinger, Alessia$$b1
000290535 7001_ $$aSchniederjohann, Christina$$b2
000290535 7001_ $$aRoider, Tobias$$b3
000290535 7001_ $$00000-0002-6010-1220$$aCoelho, Mariana$$b4
000290535 7001_ $$0P:(DE-He78)e73a0a4fab40344d89d693cbe1df3109$$aMack, Norman$$b5
000290535 7001_ $$00000-0002-9992-3109$$aBruch, Peter-Martin$$b6
000290535 7001_ $$aLiebers, Nora$$b7
000290535 7001_ $$aDötsch, Sarah$$b8
000290535 7001_ $$00000-0001-8713-093X$$aBusch, Dirk H$$b9
000290535 7001_ $$0P:(DE-HGF)0$$aSchmitt, Michael$$b10
000290535 7001_ $$aNeumann, Frank$$b11
000290535 7001_ $$0P:(DE-HGF)0$$aRoessner, Philipp M$$b12
000290535 7001_ $$0P:(DE-He78)e67f907703fcb2cf909f4d72d50268b5$$aSeiffert, Martina$$b13
000290535 7001_ $$aDietrich, Sascha$$b14
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