Therapeutic targeting of Notch signaling and immune checkpoint blockade in a spontaneous, genetically heterogeneous mouse model of T-cell acute lymphoblastic leukemia.
Animals
Antibodies, Monoclonal
/ metabolism
B7-H1 Antigen
/ metabolism
Disease Models, Animal
Gene Deletion
Humans
Immunotherapy
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Transgenic
Molecular Targeted Therapy
Mutation
/ genetics
Oncogenes
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
/ genetics
Receptors, Notch
/ metabolism
Signal Transduction
Thymus Gland
/ transplantation
Immunotherapy
Notch1
PD-1 blockade
T-ALL
Targeted therapy
Journal
Disease models & mechanisms
ISSN: 1754-8411
Titre abrégé: Dis Model Mech
Pays: England
ID NLM: 101483332
Informations de publication
Date de publication:
16 09 2019
16 09 2019
Historique:
received:
10
06
2019
accepted:
29
07
2019
pubmed:
11
8
2019
medline:
23
5
2020
entrez:
11
8
2019
Statut:
epublish
Résumé
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic cancer derived from the malignant transformation of T-cell progenitors. Outcomes remain poor for T-ALL patients who have either primary resistance to standard-of-care chemotherapy or disease relapse. Notably, there are currently no targeted therapies available in T-ALL. This lack of next-generation therapies highlights the need for relevant preclinical disease modeling to identify and validate new targets and treatment approaches. Here, we adapted a spontaneously arising, genetically heterogeneous, thymic transplantation-based murine model of T-ALL, recapitulating key histopathological and genetic features of the human disease, to the preclinical testing of targeted and immune-directed therapies. Genetic engineering of the murine
Identifiants
pubmed: 31399482
pii: dmm.040931
doi: 10.1242/dmm.040931
pmc: PMC6765191
pii:
doi:
Substances chimiques
Antibodies, Monoclonal
0
B7-H1 Antigen
0
Receptors, Notch
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2019. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interestsAll authors are employees of Regeneron Pharmaceuticals.
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