Targeting B cell lymphoma with interferon alpha (IFNɑ) fused to an anti-CD20 antibody eliminated the cancer’s resistance to anti-CD20 therapy in murine models because the inclusion of IFNɑ converted cancer cells into potent antigen-presenting cells that re-activated CD8+ tumor infiltrating lymphocytes, which then targeted and killed the cancer cells.
Anti-hCD20 is a therapeutic monoclonal antibody (mAb) that is clinically used to treat B-cell lymphoma. Some lymphomas are resistant to anti-hCD20; others relapse after treatment with anti-hCD20. Using a syngeneic immunocompetent mouse model, we observed that targeting lymphoma with interferon-alpha (IFNalpha) abolished resistance of B-cell lymphoma to anti-CD20 while limiting interferon (IFN)-associated systemic toxicity in the host. Control of tumors by a fusion of anti-CD20 and IFNalpha (anti-CD20-IFNalpha) depended on existing tumor-infiltrating CD8+ T cells. Although lymphomas were resistant to IFN-directed killing, IFN-exposed tumor cells became the dominant antigen-presenting cells (APCs) for the reactivation of tumor-infiltrating CD8+ T cells that then controlled those lymphomas. Moreover, anti-CD20-IFNalpha abolished checkpoint blockade resistance in advanced B-cell lymphoma. Our findings indicate that anti-CD20-IFNalpha eradicates B-cell lymphoma by employing tumor cells as APCs to reactivate tumor-infiltrating CD8+ T cells and synergizing with anti-PD-L1 treatment.
Author Info: (1) Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences. (2) DingFu Biotarget Co. Ltd. (3) Key Laboratory of Infection and Immunit
Author Info: (1) Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences. (2) DingFu Biotarget Co. Ltd. (3) Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences. (4) Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences. (5) Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences. (6) Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences. (7) Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences. (8) University of Chinese Academy of Sciences. (9) Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences. (10) Pathology, University of Texas Southwestern Medical Center yang-xin.fu@utsouthwestern.edu.
