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Activity of tafasitamab in combination with rituximab in subtypes of aggressive lymphoma

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064165%3A_____%2F23%3A10467382" target="_blank" >RIV/00064165:_____/23:10467382 - isvavai.cz</a>

  • Alternative codes found

    RIV/00216208:11110/23:10467382

  • Result on the web

    <a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=C2ptCjbqan" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=C2ptCjbqan</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.3389/fimmu.2023.1220558" target="_blank" >10.3389/fimmu.2023.1220558</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Activity of tafasitamab in combination with rituximab in subtypes of aggressive lymphoma

  • Original language description

    Background: Despite recent advances in the treatment of aggressive lymphomas, a significant fraction of patients still succumbs to their disease. Thus, novel therapies are urgently needed. As the anti-CD20 antibody rituximab and the CD19-targeting antibody tafasitamab share distinct modes of actions, we investigated if dual-targeting of aggressive lymphoma B-cells by combining rituximab and tafasitamab might increase cytotoxic effects. Methods: Antibody single and combination efficacy was determined investigating different modes of action including direct cytotoxicity, antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) in in vitro and in vivo models of aggressive B-cell lymphoma comprising diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL). Results: Three different sensitivity profiles to antibody monotherapy or combination treatment were observed in in vitro models: while 1/11 cell lines was primarily sensitive to tafasitamab and 2/11 to rituximab, the combination resulted in enhanced cell death in 8/11 cell lines in at least one mode of action. Treatment with either antibody or the combination resulted in decreased expression of the oncogenic transcription factor MYC and inhibition of AKT signaling, which mirrored the cell line-specific sensitivities to direct cytotoxicity. At last, the combination resulted in a synergistic survival benefit in a PBMC-humanized Ramos NOD/SCID mouse model. Conclusion: This study demonstrates that the combination of tafasitamab and rituximab improves efficacy compared to single-agent treatments in models of aggressive B-cell lymphoma in vitro and in vivo.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    30205 - Hematology

Result continuities

  • Project

  • Continuities

    V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Others

  • Publication year

    2023

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    Frontiers in Immunology

  • ISSN

    1664-3224

  • e-ISSN

    1664-3224

  • Volume of the periodical

    14

  • Issue of the periodical within the volume

    July

  • Country of publishing house

    CH - SWITZERLAND

  • Number of pages

    14

  • Pages from-to

    1220558

  • UT code for WoS article

    001047490900001

  • EID of the result in the Scopus database

    2-s2.0-85168111492