title: Investigational therapies targeting lymphocyte antigens for the treatment of non-Hodgkin's lymphoma.
abstract: BACKGROUND
  The advent of the anti-CD20 mAb rituximab has opened a new era in the treatment of non-Hodgkin's lymphomas (NHL), markedly altering standard treatment strategies. Moreover, the proof-of-concept that targeting a specific lymphocyte surface antigen may induce a highly effective and safe targeted killing of malignant cells has opened the door to the development of a plethora of novel mAbs directed towards different B- and T-cell-specific antigens.
  
  
  METHODS
  This review discusses the recent available clinical data about new-generation anti-CD20 mAbs characterized by increased antibody- (obinutuzumab) or complement-dependent cyotoxicity (ofatumumab) as well as novel investigational agents targeting other lymphocyte antigens (e.g., CD19, CD22, CD30, CD40, CD52, CCR4), which are currently under investigation for B- and T-cell NHL treatment. In addition, antibody-drug conjugates (inotuzumab ozogamicin, brentuximab vedotin, polatuzumab vedotin), bispecific T-cell engagers (blinatumomab) and a new class of antibodies targeting cytotoxic T-lymphocyte-associated antigen 4, programmed death 1 or programmed death ligand 1 (immune checkpoint inhibitors) are specifically considered.
  
  
  CONCLUSIONS
  Among the novel mAbs challenging rituximab, obinutuzumab seems to be in the most advanced phase, with the results of randomized trials awaited shortly. Brentuximab vedotin is increasing its role in T-cell NHL. Furthermore, immune checkpoint inhibitors have the potential to acquire a great relevance in NHL therapy.
authors.affiliation: University Hospital Ospedale di Circolo and Fondazione Macchi, Division of Hematology , Viale L. Borri 57, 21100 Varese , Italy +39 332 393 648 ; francesco.passamonti@ospedale.varese.it.
authors.forename: Michele
authors.initials: M
authors.lastname: Merli
authors.forename: Andrea
authors.initials: A
authors.lastname: Ferrario
authors.forename: Margherita
authors.initials: M
authors.lastname: Maffioli
authors.forename: Luca
authors.initials: L
authors.lastname: Arcaini
authors.forename: Francesco
authors.initials: F
authors.lastname: Passamonti
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000954:Antigens, Surface / Q000276:immunology*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D035703:Therapies, Investigational
chemical_list: D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D000970:Antineoplastic Agents; D018796:Immunoconjugates
keywords: CD20; CD30; CTLA-4; PD-1; PD-L1; antibody–drug conjugates; bispecific T-cell engagers; immune checkpoint inhibitors; mAb; non-Hodgkin’s lymphoma