Rituximab-IgG2 is a phagocytic enhancer in antibody-based immunotherapy of B-cell lymphoma by altering CD47 expression
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 imm...
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Frontiers Media S.A.
2024-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1483617/full |
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| author | Oanh T. P. Nguyen Sandra Lara Giovanni Ferro Matthias Peipp Sandra Kleinau |
| author_facet | Oanh T. P. Nguyen Sandra Lara Giovanni Ferro Matthias Peipp Sandra Kleinau |
| author_sort | Oanh T. P. Nguyen |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-89cbae7d553a4901a0c53c5d3f712f6b |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-89cbae7d553a4901a0c53c5d3f712f6b2024-12-06T06:50:54ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-12-011510.3389/fimmu.2024.14836171483617Rituximab-IgG2 is a phagocytic enhancer in antibody-based immunotherapy of B-cell lymphoma by altering CD47 expressionOanh T. P. Nguyen0Sandra Lara1Giovanni Ferro2Matthias Peipp3Sandra Kleinau4Department of Cell and Molecular Biology, Uppsala University, Uppsala, SwedenDepartment of Cell and Molecular Biology, Uppsala University, Uppsala, SwedenDepartment of Cell and Molecular Biology, Uppsala University, Uppsala, SwedenDivision of Antibody-Based Immunotherapy, University Hospital Schleswig-Holstein, Kiel, GermanyDepartment of Cell and Molecular Biology, Uppsala University, Uppsala, SwedenAntibody-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.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1483617/fullanti-CD20 antibodyapoptosisCD47cancer immunotherapymonocytephagocytosis |
| spellingShingle | Oanh T. P. Nguyen Sandra Lara Giovanni Ferro Matthias Peipp Sandra Kleinau Rituximab-IgG2 is a phagocytic enhancer in antibody-based immunotherapy of B-cell lymphoma by altering CD47 expression Frontiers in Immunology anti-CD20 antibody apoptosis CD47 cancer immunotherapy monocyte phagocytosis |
| title | Rituximab-IgG2 is a phagocytic enhancer in antibody-based immunotherapy of B-cell lymphoma by altering CD47 expression |
| title_full | Rituximab-IgG2 is a phagocytic enhancer in antibody-based immunotherapy of B-cell lymphoma by altering CD47 expression |
| title_fullStr | Rituximab-IgG2 is a phagocytic enhancer in antibody-based immunotherapy of B-cell lymphoma by altering CD47 expression |
| title_full_unstemmed | Rituximab-IgG2 is a phagocytic enhancer in antibody-based immunotherapy of B-cell lymphoma by altering CD47 expression |
| title_short | Rituximab-IgG2 is a phagocytic enhancer in antibody-based immunotherapy of B-cell lymphoma by altering CD47 expression |
| title_sort | rituximab igg2 is a phagocytic enhancer in antibody based immunotherapy of b cell lymphoma by altering cd47 expression |
| topic | anti-CD20 antibody apoptosis CD47 cancer immunotherapy monocyte phagocytosis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1483617/full |
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