title: Improving therapeutic activity of anti-CD20 antibody therapy through immunomodulation in lymphoid malignancies.
abstract: Nearly two decades ago rituximab heralded a new era in management of B cell malignancies significantly increasing response rates and survival. However, despite clear therapeutic advantage, significant numbers of patients become refractory to anti-CD20 mAb therapy, suggesting urgent improvements are required. It is now well recognized that the suppressive tumor microenvironment plays an important role in the outcome of anti-CD20 mAb therapy and that manipulation of this environment may improve the efficacy and produce long-term tumor control. The past few years have seen a surge of interest in immunomodulatory agents capable of overwriting immune suppressive networks into favorable clinical outcome. Currently, a number of such combinations with anti-CD20 mAb is under evaluation and some have produced encouraging outcomes in rituximab refractory disease. In this review, we give an outline of anti-CD20 mAbs and explore the combinations with immunomodulatory agents that enhance antitumor immunity through targeting stimulatory or inhibitory pathways and have proven potential to synergize with anti-CD20 mAb therapy. These agents, primarily mAbs, target CTLA-4, PD-1/PD-L1, and CD40.
authors.affiliation: a Targeted Therapy Group, Institute of Cancer Sciences, University of Manchester, Manchester Cancer Research Centre, Manchester Academic Health Sciences Centre , Manchester , UK.
authors.forename: Grazyna
authors.initials: G
authors.lastname: Lipowska-Bhalla
authors.affiliation: a Targeted Therapy Group, Institute of Cancer Sciences, University of Manchester, Manchester Cancer Research Centre, Manchester Academic Health Sciences Centre , Manchester , UK.
authors.forename: Ester
authors.initials: E
authors.lastname: Fagnano
authors.affiliation: a Targeted Therapy Group, Institute of Cancer Sciences, University of Manchester, Manchester Cancer Research Centre, Manchester Academic Health Sciences Centre , Manchester , UK.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Illidge
authors.affiliation: a Targeted Therapy Group, Institute of Cancer Sciences, University of Manchester, Manchester Cancer Research Centre, Manchester Academic Health Sciences Centre , Manchester , UK.
authors.forename: Eleanor J
authors.initials: EJ
authors.lastname: Cheadle
mesh_terms: D000818:Animals; D018951:Antigens, CD20; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors; D019013:CD40 Antigens / Q000037:antagonists & inhibitors; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use*; D056747:Immunomodulation / Q000187:drug effects*; D015448:Leukemia, B-Cell / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D058990:Molecular Targeted Therapy; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors; D000069283:Rituximab / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018951:Antigens, CD20; D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; D019013:CD40 Antigens; D060908:CTLA-4 Antigen; D007155:Immunologic Factors; D061026:Programmed Cell Death 1 Receptor; D000069283:Rituximab
keywords: Anti-CD20; CTLA-4; rituximab