Daratumumab Immunopolymersome-Enabled Safe and CD38-Targeted Chemotherapy and Depletion of Multiple Myeloma.
Adv Mater
; 33(39): e2007787, 2021 Oct.
Article
in En
| MEDLINE
| ID: mdl-34369013
ABSTRACT
Multiple myeloma (MM) is a second ranking hematological malignancy. Despite the fast advancement of new treatments such as bortezormib and daratumumab, MM patients remain incurable and tend to eventually become relapsed and drug-resistant. Development of novel therapies capable of depleting MM cells is strongly needed. Here, daratumumab immunopolymersomes carrying vincristine sulfate (Dar-IPs-VCR) are reported for safe and high-efficacy CD38-targeted chemotherapy and depletion of orthotopic MM in vivo. Dar-IPs-VCR made by postmodification via strain-promoted click reaction holds tailored antibody density (2.2, 4.4 to 8.7 Dar per IPs), superb stability, small size (43-49 nm), efficacious VCR loading, and glutathione-responsive VCR release. Dar4.4 -IPs-VCR induces exceptional anti-MM activity with an IC50 of 76 × 10-12 m to CD38-positive LP-1 MM cells, 12- and 20-fold enhancement over nontargeted Ps-VCR and free VCR controls, respectively. Intriguingly, mice bearing orthotopic LP-1-Luc MM following four cycles of i.v. administration of Dar4.4 -IPs-VCR at 0.25 mg VCR equiv. kg-1 reveal complete depletion of LP-1-Luc cells, superior survival rate to all controls, and no body weight loss. The bone and histological analyses indicate bare bone and organ damage. Dar-IPs-VCR appears as a safe and targeted treatment for CD38-overexpressed hematological malignancies.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
ADP-ribosyl Cyclase 1
/
Antibodies, Monoclonal
/
Multiple Myeloma
/
Antineoplastic Agents, Phytogenic
Limits:
Animals
/
Humans
Language:
En
Journal:
Adv Mater
Journal subject:
BIOFISICA
/
QUIMICA
Year:
2021
Document type:
Article