A non-internalised CD38-binding radiolabelled single-domain antibody fragment to monitor and treat multiple myeloma.
CD38
Multiple myeloma
Nanobody
Radio-immunotherapy
Single-domain antibody
Targeted radionuclide therapy
Theranostic
Journal
Journal of hematology & oncology
ISSN: 1756-8722
Titre abrégé: J Hematol Oncol
Pays: England
ID NLM: 101468937
Informations de publication
Date de publication:
02 11 2021
02 11 2021
Historique:
received:
30
06
2021
accepted:
22
09
2021
entrez:
3
11
2021
pubmed:
4
11
2021
medline:
8
2
2022
Statut:
epublish
Résumé
Antibody-based therapies targeting CD38 are currently used as single agents as well as in combination regimens for multiple myeloma, a malignant plasma cell disorder. In this study, we aimed to develop anti-CD38 single-domain antibodies (sdAbs) that can be used to trace CD38 Four different anti-CD38 sdAbs were produced, and their binding affinities and potential competition with the monoclonal antibody daratumumab were tested using biolayer interferometry. Their binding kinetics and potential cell internalisation were further studied after radiolabelling with the diagnostic radioisotope Indium-111. The resulting radiotracers were evaluated in vivo for their tumour-targeting potential and biodistribution through single-photon emission computed tomography (SPECT/CT) imaging and serial dissections. Finally, therapeutic efficacy of a lead anti-CD38 sdAb, radiolabelled with the therapeutic radioisotope Lutetium-177, was evaluated in a CD38 These results highlight the theranostic potential of radiolabelled anti-CD38 sdAbs for the monitoring and treatment of multiple myeloma.
Sections du résumé
BACKGROUND
Antibody-based therapies targeting CD38 are currently used as single agents as well as in combination regimens for multiple myeloma, a malignant plasma cell disorder. In this study, we aimed to develop anti-CD38 single-domain antibodies (sdAbs) that can be used to trace CD38
METHODS
Four different anti-CD38 sdAbs were produced, and their binding affinities and potential competition with the monoclonal antibody daratumumab were tested using biolayer interferometry. Their binding kinetics and potential cell internalisation were further studied after radiolabelling with the diagnostic radioisotope Indium-111. The resulting radiotracers were evaluated in vivo for their tumour-targeting potential and biodistribution through single-photon emission computed tomography (SPECT/CT) imaging and serial dissections. Finally, therapeutic efficacy of a lead anti-CD38 sdAb, radiolabelled with the therapeutic radioisotope Lutetium-177, was evaluated in a CD38
CONCLUSIONS
These results highlight the theranostic potential of radiolabelled anti-CD38 sdAbs for the monitoring and treatment of multiple myeloma.
Identifiants
pubmed: 34727950
doi: 10.1186/s13045-021-01171-6
pii: 10.1186/s13045-021-01171-6
pmc: PMC8561907
doi:
Substances chimiques
Radioisotopes
0
Single-Domain Antibodies
0
Lutetium
5H0DOZ21UJ
Lutetium-177
BRH40Y9V1Q
ADP-ribosyl Cyclase 1
EC 3.2.2.6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
183Informations de copyright
© 2021. The Author(s).
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