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

Autor: Astri Maaland, Jostein Dahle, Arne Kolstad, Tania Stallons, Amal Saidi, Julien Torgue, Helen Heyerdahl
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Oncology
Radioimmunoconjugate
Physiology
Tetraspanins
Cell Lines
Cancer Treatment
Cetuximab
Mice
SCID
Toxicology
Pathology and Laboratory Medicine
Mice
0302 clinical medicine
Antineoplastic Agents
Immunological
Animal Cells
hemic and lymphatic diseases
Medicine and Health Sciences
Neoplasm
0303 health sciences
Multidisciplinary
Hematology
Lymphoma
Non-Hodgkin
Animal Models
Lead Radioisotopes
Body Fluids
Leukemia
Blood
Experimental Organism Systems
030220 oncology & carcinogenesis
Toxicity
Medicine
Female
Biological Cultures
Anatomy
Cellular Types
Research Article
Platelets
medicine.medical_specialty
Science
Mouse Models
Daudi Cells
Research and Analysis Methods
03 medical and health sciences
Model Organisms
Antigens
Neoplasm
Internal medicine
Cell Line
Tumor
medicine
Animals
Humans
Radiometry
030304 developmental biology
Cell Proliferation
Blood Cells
business.industry
Euthanasia
Therapeutic effect
Biology and Life Sciences
Kidneys
Cell Biology
Renal System
medicine.disease
Non-Hodgkin's lymphoma
Lymphoma
Leukemia
Lymphoid
Animal Studies
business
Zdroj: PLoS ONE
PLoS ONE, Vol 15, Iss 3, p e0230526 (2020)
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: