Nordic Nanovector ASA, Oslo, Norway.
Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
Eur J Haematol. 2018 Oct;101(4):522-531. doi: 10.1111/ejh.13139. Epub 2018 Aug 31.
To investigate the therapeutic potential of the next-generation anti-CD37 radioimmunoconjugate Lu-lilotomab satetraxetan ( Lu-lilotomab) in combination with the anti-CD20 antibody rituximab for treatment of mice with non-Hodgkin's lymphoma (NHL) xenografts.
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 Lu-lilotomab or rituximab alone or with the combination of both treatments. Tumour volume, body weight, blood counts and clinical status were monitored. CD20 expression was measured using flow cytometry with fluorescence-labelled rituximab.
The combination of 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 Lu-lilotomab.
Treatment of mice with NHL xenografts with Lu-lilotomab synergistically increased tumour suppression of subsequent anti-CD20 immunotherapy and improved survival. If the same effect is confirmed in a recently started clinical study, it could change the way radioimmunotherapy and CD20 immunotherapy would be used in the future.
研究新一代抗 CD37 放射性免疫偶联物 Lu-lilotomab satetraxetan（Lu-lilotomab）与抗 CD20 抗体利妥昔单抗联合用于治疗非霍奇金淋巴瘤（NHL）异种移植瘤小鼠的治疗潜力。
皮下（s.c.）Burkitt 淋巴瘤 Daudi 异种移植瘤裸鼠和静脉内（i.v.）注射套细胞淋巴瘤 Rec-1 细胞的 SCID 小鼠分别单独用 Lu-lilotomab 或利妥昔单抗或两种治疗方法联合治疗。监测肿瘤体积、体重、血细胞计数和临床状况。使用荧光标记的利妥昔单抗通过流式细胞术测量 CD20 表达。
Lu-lilotomab 和利妥昔单抗联合治疗皮下 Daudi 异种移植瘤裸鼠具有协同作用，而对静脉注射 Rec-1 细胞的 SCID 小鼠则具有相加作用。Lu-lilotomab 预处理可增加利妥昔单抗与 NHL 细胞的体外结合。
Lu-lilotomab 治疗 NHL 异种移植瘤小鼠可协同增强随后的抗 CD20 免疫治疗的肿瘤抑制作用，并提高生存率。如果在最近开始的一项临床研究中证实了相同的效果，它可能会改变放射性免疫治疗和 CD20 免疫治疗未来的应用方式。
