Skip to main content

ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1483617
This article is part of the Research Topic Innovative Immunotherapy Strategies for Enhanced Treatment of Hodgkin and Non-Hodgkin Lymphomas View all 9 articles

Rituximab-IgG2 is a phagocytic enhancer in antibody-based immunotherapy of B-cell lymphoma by altering CD47 expression

Provisionally accepted
Oanh T. P. Nguyen Oanh T. P. Nguyen 1Sandra Lara Sandra Lara 1Giovanni Ferro Giovanni Ferro 1Matthias Peipp Matthias Peipp 2Sandra Kleinau Sandra Kleinau 1*
  • 1 Uppsala University, Uppsala, Sweden
  • 2 University Medical Center Schleswig-Holstein, Kiel, Schleswig-Holstein, Germany

The final, formatted version of the article will be published soon.

    Antibody-dependent cellular phagocytosis (ADCP) by monocytes and macrophages contributes significantly to the efficacy of many therapeutic monoclonal antibodies (mAbs), including anti-CD20 rituximab (RTX) targeting CD20 + B-cell non-Hodgkin lymphomas (NHL). However, ADCP is constrained by various immune checkpoints, notably the anti-phagocytic CD47 molecule, necessitating strategies to overcome this resistance. We have previously shown that the IgG2 isotype of RTX induces CD20-mediated apoptosis in B-cell lymphoma cells and, when combined with RTX-IgG1 or RTX-IgG3 mAbs, can significantly enhance Fc receptor-mediated phagocytosis. Here, we report that the apoptotic effect of RTX-IgG2 on lymphoma cells contributes to changes in the tumor cell's CD47 profile by reducing its overall expression and altering its surface distribution. Furthermore, when RTX-IgG2 is combined with other lymphoma-targeting mAbs, such as anti-CD59 or anti-PD-L1, it significantly enhances the ADCP of lymphoma cells compared to single mAb treatment. In summary, RTX-IgG2 acts as a potent phagocytic enhancer by promoting Fc-receptor mediated phagocytosis through apoptosis and reduction of CD47 in CD20 + malignant B-cells. RTX-IgG2 represents a valuable therapeutic component in enhancing the effectiveness of different mAbs targeting B-cell NHL.

    Keywords: Anti-CD20 antibody, Apoptosis, cd47, cancer immunotherapy, monocyte, Phagocytosis, rituximab

    Received: 20 Aug 2024; Accepted: 14 Nov 2024.

    Copyright: © 2024 Nguyen, Lara, Ferro, Peipp and Kleinau. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Sandra Kleinau, Uppsala University, Uppsala, Sweden

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.