Targeted alpha therapy for chronic lymphocytic leukaemia and non-Hodgkin's lymphoma with the anti-CD37 radioimmunoconjugate 212Pb-NNV003.

Relapse of chronic lymphocytic leukaemia and non-Hodgkin's lymphoma after standard of care treatment is common and new therapies are needed. The targeted alpha therapy with 212Pb-NNV003 presented in this study combines cytotoxic α-particles from 212Pb, with the anti-CD37 antibody NNV003, targeting B-cell malignancies. The goal of this study was to explore 212Pb-NNV003 for treatment of CD37 positive chronic lymphocytic leukaemia and non-Hodgkin's lymphoma in preclinical mouse models.An anti-proliferative effect of 212Pb-NNV003 was observed in both chronic lymphocytic leukaemia (MEC-2) and Burkitt's lymphoma (Daudi) cells in vitro. In biodistribution experiments, accumulation of 212Pb-NNV003 was 23%ID/g and 16%ID/g in Daudi and MEC-2 tumours 24 h post injection. In two intravenous animal models 90% of the mice treated with a single injection of 212Pb-NNV003 were alive 28 weeks post cell injection. Median survival times of control groups were 5-9 weeks. There was no significant difference between different specific activities of 212Pb-NNV003 with regards to therapeutic effect or toxicity. For therapeutically effective activities, a transient haematological toxicity was observed. This study shows that 212Pb-NNV003 is effective and safe in preclinical models of CD37 positive chronic lymphocytic leukaemia and non-Hodgkin's lymphoma, warranting future clinical testing.

Déclaration de conflit d'intérêts

I have read the journal's policy and the authors of this manuscript have the following competing interests: JD and HH are employees and shareholders of Nordic Nanovector ASA. AFM is a PhD student employed by Nordic Nanovector ASA, funded by the Norwegian Research Council. AK is a member of the Scientific Advisory Board of Nordic Nanovector ASA. AS is employed by Orano Med SAS, TARS and JT are employed by Orano Med LLC. Patents: PCT/EP2011/051231 (Radioimmunoconjugates and uses thereof), PCT/EP2014/061824 (Method for upregulating antigen expression), PCT/EP2017/073336 (Treatment of non-Hodgkin lymphoma using lilotomab and 177Lu-lilotomab satetraxetan), PCT/EP2018/082065 (Radioimmunoconjugates in combination with other drugs as treatment against NHL), EP2854870B1 (Method and apparatus for the production of lead 212 for medical use), EP3174068B1 (New method and apparatus for the production of high purity radionuclides). This does not alter our adherence to PLOS ONE policies on sharing data and materials.