Open AccessTargeted alpha therapy for chronic lymphocytic leukaemia and non-Hodgkin’s lymphoma with the anti-CD37 radioimmunoconjugate 212Pb-NNV003
Author(s) -
Astri Fjelde Maaland,
Amal Saidi,
Julien Torgue,
Helèn Heyerdahl,
Tania A. Rozgaja Stallons,
Arne Kolstad,
Jostein Dahle
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0230526
Subject(s) - medicine , lymphoma , chronic lymphocytic leukemia , toxicity , immunology , non hodgkin's lymphoma , hematology , radioimmunotherapy , cancer research , oncology , leukemia , pathology , antibody , monoclonal antibody
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 212 Pb-NNV003 presented in this study combines cytotoxic α-particles from 212 Pb, with the anti-CD37 antibody NNV003, targeting B-cell malignancies. The goal of this study was to explore 212 Pb-NNV003 for treatment of CD37 positive chronic lymphocytic leukaemia and non-Hodgkin’s lymphoma in preclinical mouse models.An anti-proliferative effect of 212 Pb-NNV003 was observed in both chronic lymphocytic leukaemia (MEC-2) and Burkitt’s lymphoma (Daudi) cells in vitro . In biodistribution experiments, accumulation of 212 Pb-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 212 Pb-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 212 Pb-NNV003 with regards to therapeutic effect or toxicity. For therapeutically effective activities, a transient haematological toxicity was observed. This study shows that 212 Pb-NNV003 is effective and safe in preclinical models of CD37 positive chronic lymphocytic leukaemia and non-Hodgkin’s lymphoma, warranting future clinical testing.