The B7-H3-Targeting Antibody-Drug Conjugate m276-SL-PBD Is Potently Effective Against Pediatric Cancer Preclinical Solid Tumor Models.
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
15 05 2021
15 05 2021
Historique:
received:
03
11
2020
revised:
07
01
2021
accepted:
15
02
2021
pubmed:
24
2
2021
medline:
17
3
2022
entrez:
23
2
2021
Statut:
ppublish
Résumé
Patients with relapsed pediatric solid malignancies have few therapeutic options, and many of these patients die of their disease. B7-H3 is an immune checkpoint protein encoded by the B7-H3 expression was quantified by RNA sequencing and by IHC on pediatric PDX microarrays. We tested the safety and efficacy of m276-SL-PBD in two stages. Randomized trials of m276-SL-PBD of 0.5 mg/kg on days 1, 8, and 15 compared with vehicle were performed in PDX or CDX models of Ewing sarcoma ( The vast majority of PDX and CDX samples studied showed intense membranous B7-H3 expression (median H-score 177, SD 52). In the randomized trials, m276-SL-PBD showed a 92.3% response rate, with 61.5% of models showing a maintained complete response (MCR). These data were confirmed in the single mouse trial with an overall response rate of 91.5% and MCR rate of 64.4%. Treatment-related mortality rate was 5.5% with late weight loss observed in a subset of models dosed once a week for 3 weeks. m276-SL-PBD has significant antitumor activity across a broad panel of pediatric solid tumor PDX models.
Identifiants
pubmed: 33619171
pii: 1078-0432.CCR-20-4221
doi: 10.1158/1078-0432.CCR-20-4221
pmc: PMC8127361
mid: NIHMS1678396
doi:
Substances chimiques
B7 Antigens
0
CD276 protein, human
0
Immunoconjugates
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2938-2946Subventions
Organisme : NCI NIH HHS
ID : F31 CA254244
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA199287
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA263981
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA220500
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA199222
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA199221
Pays : United States
Organisme : NCI NIH HHS
ID : F31 CA239424
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA199297
Pays : United States
Informations de copyright
©2021 American Association for Cancer Research.
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