title: T and NK cells of B cell NHL patients exert cytotoxicity against lymphoma cells following binding of bispecific tetravalent antibody CD19 × CD3 or CD19 × CD16.
abstract: Bispecific tetravalent antibodies (TandAb) directed against the B cell surface marker CD19 and activating receptors on T or NK cells (CD19 × CD3 or CD19 × CD16) have shown promising effects in vitro and in preclinical studies. Here, we examine the cytotoxic efficacy of T and NK cells from patients with B cell Non-Hodgkin's Lymphoma (NHL) against B-lymphoma cells following the binding of the matching TandAb. The addition of CD19 × CD16 TandAb led to a threefold increase in NK cell activation in the presence of B-lymphoma cells. Similarly, T cells displayed a sevenfold increase in cytotoxic activity after the addition of CD19 × CD3 TandAb. Comparison of T and NK cell effector function of patients and healthy controls showed comparable levels of cytotoxic activity in response to lymphoma cells and no reduction in functional activity due to age, disease stage or the type and amount of previous therapy. Thus, T and NK cells of patients with B cell NHL are fully capable of being activated by therapeutic crosslinking antibodies. These results provide a rationale for the use of TandAbs for patients with B cell NHL, particularly in cases where remission with minimal residual disease could be achieved by cytotoxic chemotherapy.
authors.affiliation: Department of Hematology, Oncology and Clinical Immunology, Heinrich-Heine-University, Düsseldorf, Germany. Lisa.Poertner@uni-duesseldorf.de
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Pörtner
authors.forename: Kathrin
authors.initials: K
authors.lastname: Schönberg
authors.forename: Maryam
authors.initials: M
authors.lastname: Hejazi
authors.forename: Daniela
authors.initials: D
authors.lastname: Brünnert
authors.forename: Frank
authors.initials: F
authors.lastname: Neumann
authors.forename: Lars
authors.initials: L
authors.lastname: Galonska
authors.forename: Uwe
authors.initials: U
authors.lastname: Reusch
authors.forename: Melvyn
authors.initials: M
authors.lastname: Little
authors.forename: Rainer
authors.initials: R
authors.lastname: Haas
authors.forename: Markus
authors.initials: M
authors.lastname: Uhrberg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018033:Antibodies, Bispecific / Q000276:immunology / Q000494:pharmacology*; D018941:Antigens, CD19 / Q000276:immunology; D000970:Antineoplastic Agents / Q000276:immunology / Q000494:pharmacology*; D017252:CD3 Complex / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D058851:GPI-Linked Proteins / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D017452:Receptors, IgG / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D018033:Antibodies, Bispecific; D018941:Antigens, CD19; D000970:Antineoplastic Agents; D017252:CD3 Complex; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D017452:Receptors, IgG