Immunomodulatory properties of CD38 antibodies and their effect on anticancer efficacy in multiple myeloma.
CD38 antibodies
adenosine
bone marrow niche
daratumumab
immunomodulation
isatuximab
multiple myeloma
Journal
Cancer medicine
ISSN: 2045-7634
Titre abrégé: Cancer Med
Pays: United States
ID NLM: 101595310
Informations de publication
Date de publication:
Oct 2023
Oct 2023
Historique:
revised:
20
09
2023
received:
04
08
2023
accepted:
22
09
2023
medline:
27
11
2023
pubmed:
16
10
2023
entrez:
16
10
2023
Statut:
ppublish
Résumé
CD38 has been established as an important therapeutic target for multiple myeloma (MM), for which two CD38 antibodies are currently approved-daratumumab and isatuximab. CD38 is an ectoenzyme that degrades NAD and its precursors and is involved in the production of adenosine and other metabolites. Among the various mechanisms by which CD38 antibodies can induce MM cell death is immunomodulation, including multiple pathways for CD38-mediated T-cell activation. Patients who respond to anti-CD38 targeting treatment experience more marked changes in T-cell expansion, activity, and clonality than nonresponders. Resistance mechanisms that undermine the immunomodulatory effects of CD38-targeting therapies can be tumor intrinsic, such as the downregulation of CD38 surface expression and expression of complement inhibitor proteins, and immune microenvironment-related, such as changes to the natural killer (NK) cell numbers and function in the bone marrow niche. There are numerous strategies to overcome this resistance, which include identifying and targeting other therapeutic targets involved in, for example, adenosine production, the activation of NK cells or monocytes through immunomodulatory drugs and their combination with elotuzumab, or with bispecific T-cell engagers.
Sections du résumé
BACKGROUND
BACKGROUND
CD38 has been established as an important therapeutic target for multiple myeloma (MM), for which two CD38 antibodies are currently approved-daratumumab and isatuximab. CD38 is an ectoenzyme that degrades NAD and its precursors and is involved in the production of adenosine and other metabolites.
AIM
OBJECTIVE
Among the various mechanisms by which CD38 antibodies can induce MM cell death is immunomodulation, including multiple pathways for CD38-mediated T-cell activation. Patients who respond to anti-CD38 targeting treatment experience more marked changes in T-cell expansion, activity, and clonality than nonresponders.
IMPLICATIONS
CONCLUSIONS
Resistance mechanisms that undermine the immunomodulatory effects of CD38-targeting therapies can be tumor intrinsic, such as the downregulation of CD38 surface expression and expression of complement inhibitor proteins, and immune microenvironment-related, such as changes to the natural killer (NK) cell numbers and function in the bone marrow niche. There are numerous strategies to overcome this resistance, which include identifying and targeting other therapeutic targets involved in, for example, adenosine production, the activation of NK cells or monocytes through immunomodulatory drugs and their combination with elotuzumab, or with bispecific T-cell engagers.
Identifiants
pubmed: 37840445
doi: 10.1002/cam4.6619
pmc: PMC10652336
doi:
Substances chimiques
ADP-ribosyl Cyclase 1
EC 3.2.2.6
Immunologic Factors
0
Adenosine
K72T3FS567
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
20332-20352Subventions
Organisme : Sanofi
Informations de copyright
© 2023 Sanofi and The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
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