Journal Article

DKFZ-2024-01152

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png CD20-bispecific antibodies improve response to CD19-CAR T-cells in lymphoma in-vitro and CLL in-vivo models.

Brinkmann, B. J. ; Floerchinger, A. ; Schniederjohann, C. ; Roider, T. ; Coelho, M. ; Mack, N.DKFZ* ; Bruch, P.-M. ; Liebers, N. ; Dötsch, S. ; Busch, D. H. ; Schmitt, M.DKFZ* ; Neumann, F. ; Roessner, P. M.DKFZ* ; Seiffert, M.DKFZ* ; Dietrich, S.

2024
American Society of Hematology Washington, DC

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Please use a persistent id in citations: doi:10.1182/blood.2023022682

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.

Note: 2024 Aug 15;144(7):784-789

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Contributing Institute(s):

1. B062 Pädiatrische Neuroonkologie (B062)
2. B060 Molekulare Genetik (B060)
3. DKTK HD zentral (HD01)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2024

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 20 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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