A Novel GUCY2C-CD3 T-Cell Engaging Bispecific Construct (PF-07062119) for the Treatment of Gastrointestinal Cancers.
Adoptive Transfer
/ methods
Animals
Antibodies, Bispecific
/ administration & dosage
CD3 Complex
/ immunology
Cell Line, Tumor
Colorectal Neoplasms
/ immunology
Disease Models, Animal
Female
Gastrointestinal Neoplasms
/ immunology
Humans
Immunotherapy
/ methods
Mice
Mice, Inbred NOD
Mice, SCID
Receptors, Enterotoxin
/ immunology
T-Lymphocytes
/ immunology
Tissue Distribution
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:
01 05 2020
01 05 2020
Historique:
received:
06
10
2019
revised:
19
12
2019
accepted:
27
01
2020
pubmed:
31
1
2020
medline:
7
2
2021
entrez:
31
1
2020
Statut:
ppublish
Résumé
Gastrointestinal cancers remain areas of high unmet need despite advances in targeted and immunotherapies. Here, we demonstrate potent, tumor-selective efficacy with PF-07062119, a T-cell engaging CD3 bispecific targeting tumors expressing Guanylyl Cyclase C (GUCY2C), which is expressed widely across colorectal cancer and other gastrointestinal malignancies. In addition, to address immune evasion mechanisms, we explore combinations with immune checkpoint blockade agents and with antiangiogenesis therapy. PF-07062119 activity was evaluated We demonstrate that GUCY2C-positive tumors can be targeted with an anti-GUCY2C/anti-CD3ε bispecific, with selective drug biodistribution to tumors. PF-07062119 showed potent T-cell-mediated These data highlight the potential for PF-07062119 to demonstrate efficacy and improve patient outcomes in colorectal cancer and other gastrointestinal malignancies.
Identifiants
pubmed: 31996389
pii: 1078-0432.CCR-19-3275
doi: 10.1158/1078-0432.CCR-19-3275
doi:
Substances chimiques
Antibodies, Bispecific
0
CD3 Complex
0
CD3E protein, human
0
GUCY2C protein, human
EC 4.6.1.2
Receptors, Enterotoxin
EC 4.6.1.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2188-2202Informations de copyright
©2020 American Association for Cancer Research.