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, target...

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Bibliographic Details
Published in:PloS one 2020, Vol.15 (3), p.e0230526-e0230526
Main Authors: Maaland, Astri Fjelde, Saidi, Amal, Torgue, Julien, Heyerdahl, Helen, Stallons, Tania A Rozgaja, Kolstad, Arne, Dahle, Jostein
Format: Article
Language:English
Subjects:
Alpha rays
Animal models
Antibodies
Biology and Life Sciences
Burkitt's lymphoma
Cancer therapies
Cell growth
Cell survival
Chemotherapy
Chronic lymphocytic leukemia
Clinical medicine
Cytotoxicity
Dosimetry
Hematology
Immunoglobulins
Injection
Intravenous administration
Leukemia
Lymphocytes B
Lymphoma
Medicine and Health Sciences
Non-Hodgkin's lymphoma
Research and Analysis Methods
Therapy
Toxicity
Tumors
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0230526