Converting Lymphoma Cells into Potent Antigen-Presenting Cells for Interferon-Induced Tumor Regression

Anti-hCD20 is a therapeutic 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 (IFN alpha) 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 IFNa (anti-CD20-IFN alpha) 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 (APC) for the reactivation of tumor-infiltrating CD8+ T cells that then controlled those lymphomas. Anti-CD20-IFN alpha also abolished checkpoint blockade resistance in advanced B-cell lymphoma. Our findings indicate that anti-CD20-IFN alpha eradicates B-cell lymphoma by employing tumor cells as APCs to reactivate tumor-infiltrating CD8(+) T cells and synergizing with anti-PD-L1 treatment. (C)2017 AACR.