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Combination of 177 Lu‐lilotomab with rituximab significantly improves the therapeutic outcome in preclinical models of non‐Hodgkin's lymphoma
Author(s) -
RepettoLlamazares Ada H. V.,
Malenge Marion M.,
O'Shea Adam,
Eiríksdóttir Bergthóra,
Stokke Trond,
Larsen Roy H.,
Dahle Jostein
Publication year - 2018
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/ejh.13139
Subject(s) - rituximab , radioimmunotherapy , medicine , cd20 , lymphoma , mantle cell lymphoma , non hodgkin's lymphoma , immunotherapy , cancer research , flow cytometry , immunology , monoclonal antibody , antibody , immune system
Objectives To investigate the therapeutic potential of the next‐generation anti‐ CD 37 radioimmunoconjugate 177 Lu‐lilotomab satetraxetan ( 177 Lu‐lilotomab) in combination with the anti‐ CD 20 antibody rituximab for treatment of mice with non‐Hodgkin's lymphoma ( NHL ) xenografts. Methods Nude mice with subcutaneous (s.c.) Burkitt's lymphoma Daudi xenografts and SCID mice intravenously (i.v.) injected with Mantle cell lymphoma Rec‐1 cells were treated with either 177 Lu‐lilotomab or rituximab alone or with the combination of both treatments. Tumour volume, body weight, blood counts and clinical status were monitored. CD 20 expression was measured using flow cytometry with fluorescence‐labelled rituximab. Results The combination of 177 Lu‐lilotomab and rituximab was synergistic for treatment of nude mice with s.c. Daudi xenografts while it was additive for treatment of SCID mice with i.v. injected Rec‐1 cells. Binding of rituximab to NHL cells in‐vitro was increased by pretreatment with 177 Lu‐lilotomab. Conclusions Treatment of mice with NHL xenografts with 177 Lu‐lilotomab synergistically increased tumour suppression of subsequent anti‐ CD 20 immunotherapy and improved survival. If the same effect is confirmed in a recently started clinical study, it could change the way radioimmunotherapy and CD 20 immunotherapy would be used in the future.