CS1-specific single-domain antibodies labeled with Actinium-225 prolong survival and increase CD8+ T cells and PD-L1 expression in Multiple Myeloma.
CS1
Multiple Myeloma
single domain antibody
targeted radionuclide therapy
Journal
Oncoimmunology
ISSN: 2162-402X
Titre abrégé: Oncoimmunology
Pays: United States
ID NLM: 101570526
Informations de publication
Date de publication:
2021
2021
Historique:
entrez:
15
11
2021
pubmed:
16
11
2021
medline:
4
1
2022
Statut:
epublish
Résumé
Multiple myeloma (MM) is a hematological malignancy characterized by the presence of clonal plasma cells in the bone marrow niche. Despite significant therapeutic advances, MM remains incurable for the majority of patients. Targeted radionuclide therapy (TRNT) has emerged as a promising treatment option to eradicate residual cancer cells. In this study, we developed and characterized single-domain antibodies (sdAbs) against the MM-antigen CS1 and evaluated its therapeutic potential in MM using TRNT. We first validated CS1 as potential target for TRNT. CS1 is expressed in normal and malignant plasma cells in different disease stages including progression and relapse. It is expressed in dormant as well as proliferating MM cells, while low expression could be observed in environmental cells. Biodistribution studies demonstrated the specific uptake of anti-CS1 sdAbs in tissues of 5TMM cell infiltration including bone, spleen and liver. TRNT using anti-CS1 sdAbs labeled with actinium-225 significantly prolonged survival of syngeneic, immunocompetent 5T33MM mice. In addition, we observed an increase in CD8
Identifiants
pubmed: 34777918
doi: 10.1080/2162402X.2021.2000699
pii: 2000699
pmc: PMC8583167
doi:
Substances chimiques
Actinium-225
0
B7-H1 Antigen
0
Signaling Lymphocytic Activation Molecule Family
0
Single-Domain Antibodies
0
Actinium
NIK1K0956U
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2000699Informations de copyright
© 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.
Déclaration de conflit d'intérêts
M.D. and N.D. are respectively employee and consultant of Precirix NV and hold ownership interest (including patents) in sdAb radiodiagnostics and radiotherapeutics. All other authors have declared no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
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