PT  - JOURNAL ARTICLE
AU  - Nguyen, Oanh T.P.
AU  - Lara, Sandra
AU  - Ferro, Giovanni
AU  - Peipp, Matthias
AU  - Kleinau, Sandra
TI  - Rituximab-IgG2 is a phagocytic enhancer in antibody-based immunotherapy of B-cell lymphoma by altering CD47 expression
AID  - 10.1101/2024.06.18.599534
DP  - 2024 Jan 01
TA  - bioRxiv
PG  - 2024.06.18.599534
4099  - http://biorxiv.org/content/early/2024/06/22/2024.06.18.599534.short
4100  - http://biorxiv.org/content/early/2024/06/22/2024.06.18.599534.full
AB  - 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 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-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.Competing Interest StatementThe authors have declared no competing interest.