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bioRxiv · 10.1101/2024.06.18.599534

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

Nguyen, O. T. P.·Lara, S.·Ferro, G.·Peipp, M.·Kleinau, S.
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Abstract

Antibody-dependent phagocytosis (ADP) 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, ADP is constrained by various immune checkpoints, notably the anti-phagocytic CD47 molecule, necessitating strategies to overcome this resistance. The IgG2 isotype of RTX induces CD20-mediated apoptosis in B-cell lymphoma cells, and significantly enhances Fc receptor-mediated phagocytosis when used in combination with RTX-IgG1 or RTX-IgG3 mAbs, as previously described. Here, we report that the apoptotic effect of RTX-IgG2 on lymphoma cells contributes to changes in the tumor cells 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-PD-L1 or anti-CD59, it significantly enhances the ADP 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 malignant CD20+ B-cells. RTX-IgG2 represents a valuable therapeutic component in enhancing the effectiveness of different mAbs targeting B-cell NHL.

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Nguyen, O. T. P., Lara, S., Ferro, G., Peipp, M., Kleinau, S.. 2024-06-22. Rituximab-IgG2 is a phagocytic enhancer in antibody-based immunotherapy of B-cell lymphoma by altering CD47 expression. https://doi.org/10.1101/2024.06.18.599534

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