Neoadjuvant Selicrelumab, an Agonist CD40 Antibody, Induces Changes in the Tumor Microenvironment in Patients with Resectable Pancreatic Cancer.
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 08 2021
15 08 2021
Historique:
received:
24
03
2021
revised:
29
04
2021
accepted:
28
05
2021
pubmed:
12
6
2021
medline:
2
4
2022
entrez:
11
6
2021
Statut:
ppublish
Résumé
CD40 activation is a novel clinical opportunity for cancer immunotherapy. Despite numerous active clinical trials with agonistic CD40 monoclonal antibodies (mAb), biological effects and treatment-related modulation of the tumor microenvironment (TME) remain poorly understood. Here, we performed a neoadjuvant clinical trial of agonistic CD40 mAb (selicrelumab) administered intravenously with or without chemotherapy to 16 patients with resectable pancreatic ductal adenocarcinoma (PDAC) before surgery followed by adjuvant chemotherapy and CD40 mAb. The toxicity profile was acceptable, and overall survival was 23.4 months (95% confidence interval, 18.0-28.8 months). Based on a novel multiplexed immunohistochemistry platform, we report evidence that neoadjuvant selicrelumab leads to major differences in the TME compared with resection specimens from treatment-naïve PDAC patients or patients given neoadjuvant chemotherapy/chemoradiotherapy only. For selicrelumab-treated tumors, 82% were T-cell enriched, compared with 37% of untreated tumors ( This unparalleled examination of CD40 mAb therapeutic mechanisms in patients provides insights for design of subsequent clinical trials targeting CD40 in cancer.
Identifiants
pubmed: 34112709
pii: 1078-0432.CCR-21-1047
doi: 10.1158/1078-0432.CCR-21-1047
pmc: PMC8667686
mid: NIHMS1715685
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Monoclonal, Humanized
0
CD40 Antigens
0
selicrelumab
0O39RGI33V
Types de publication
Clinical Trial, Phase I
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4574-4586Subventions
Organisme : NICHD NIH HHS
ID : R21 HD099367
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA224012
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA223150
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA229803
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA169123
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016520
Pays : United States
Organisme : NCI NIH HHS
ID : U2C CA233280
Pays : United States
Organisme : NCI NIH HHS
ID : UM1 CA154967
Pays : United States
Informations de copyright
©2021 The Authors; Published by the American Association for Cancer Research.
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