Improving Immunotherapy Against B-Cell Malignancies Using γδ T-Cell-specific Stimulation and Therapeutic Monoclonal Antibodies.

作者: Timm Hoeres , Dominik Pretscher , Elisabeth Holzmann , Manfred Smetak , Josef Birkmann

DOI: 10.1097/CJI.0000000000000289

关键词:

摘要: Tumor antigen-targeting monoclonal antibodies (mAbs) are an important element of current cancer therapies. Some these therapeutic mAbs enable antibody-dependent cell mediated cytotoxicity (ADCC) against tumor cells. However, cancer-related functional impairment immune effector cells may limit the clinical efficacy antibody treatments. We reckoned that combining with cell-based immunotherapies would provide a clinically relevant synergism and benefit for patients. Here, we focus on γδ T cells, as earlier studies demonstrated T-cell-based therapies safe promising several types malignancies. Similar to natural killer their antitumor effects can be enhanced using antibodies, they could, therefore, become versatile platform use variety licensed cancer. In this study, explore potential combination therapy activated rituximab more recently developed (obinutuzumab daratumumab) in different B-cell malignancies vitro. Obinutuzumab outperformed other regard direct target lysis ADCC by CD20 lines primary lymphoma specimens. demonstrate comparatively few CD16 sufficient mediate strong ADCC. Using Fc-receptor-positive lymphomas cannot blocked high concentrations immunoglobulins or anti-CD16 but both substances promote lysis. This study expands reports distinctive facilitates understanding mechanism T-cell subsets.

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