Characterization of human cancer xenografts in humanized mice.


Journal

Journal for immunotherapy of cancer
ISSN: 2051-1426
Titre abrégé: J Immunother Cancer
Pays: England
ID NLM: 101620585

Informations de publication

Date de publication:
03 2020
Historique:
accepted: 21 02 2020
entrez: 29 3 2020
pubmed: 29 3 2020
medline: 1 9 2021
Statut: ppublish

Résumé

Preclinical evaluation of drugs targeting the human immune system has posed challenges for oncology researchers. Since the commercial introduction of humanized mice, antitumor efficacy and pharmacodynamic studies can now be performed with human cancer cells within mice bearing components of a human immune system. However, development and characterization of these models is necessary to understand which model may be best suited for different agents. We characterized A375, A549, Caki-1, H1299, H1975, HCC827, HCT116, KU-19-19, MDA-MB-231, and RKO human cancer cell xenografts in CD34 We found that CD4 These data demonstrate that there are tumor-intrinsic factors that influence the immune cell repertoire within tumors and spleen, and that TIL frequencies are a key factor in determining response to anti-PD-L1 in tumor xenografts in humanized mice. These data may also aid in the selection of tumor models to test antitumor activity of novel immuno-oncology or tumor-directed agents.

Sections du résumé

BACKGROUND
Preclinical evaluation of drugs targeting the human immune system has posed challenges for oncology researchers. Since the commercial introduction of humanized mice, antitumor efficacy and pharmacodynamic studies can now be performed with human cancer cells within mice bearing components of a human immune system. However, development and characterization of these models is necessary to understand which model may be best suited for different agents.
METHODS
We characterized A375, A549, Caki-1, H1299, H1975, HCC827, HCT116, KU-19-19, MDA-MB-231, and RKO human cancer cell xenografts in CD34
RESULTS
We found that CD4
CONCLUSIONS
These data demonstrate that there are tumor-intrinsic factors that influence the immune cell repertoire within tumors and spleen, and that TIL frequencies are a key factor in determining response to anti-PD-L1 in tumor xenografts in humanized mice. These data may also aid in the selection of tumor models to test antitumor activity of novel immuno-oncology or tumor-directed agents.

Identifiants

pubmed: 32217760
pii: jitc-2019-000416
doi: 10.1136/jitc-2019-000416
pmc: PMC7174072
pii:
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: All authors are full-time employees and shareholders of Incyte.

Références

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Auteurs

Jonathan Rios-Doria (J)

Preclinical Pharmacology, Incyte Research Institute, Wilmington, Delaware, USA jdoria@incyte.com.

Christina Stevens (C)

Preclinical Pharmacology, Incyte Research Institute, Wilmington, Delaware, USA.

Christopher Maddage (C)

Preclinical Pharmacology, Incyte Research Institute, Wilmington, Delaware, USA.

Kerri Lasky (K)

Preclinical Pharmacology, Incyte Research Institute, Wilmington, Delaware, USA.

Holly K Koblish (HK)

Preclinical Pharmacology, Incyte Research Institute, Wilmington, Delaware, USA.

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Classifications MeSH