Targeting Macrophages with CAR T Cells Delays Solid Tumor Progression and Enhances Antitumor Immunity.
Journal
Cancer immunology research
ISSN: 2326-6074
Titre abrégé: Cancer Immunol Res
Pays: United States
ID NLM: 101614637
Informations de publication
Date de publication:
02 11 2022
02 11 2022
Historique:
received:
16
12
2021
revised:
17
05
2022
accepted:
08
09
2022
pubmed:
13
9
2022
medline:
4
11
2022
entrez:
12
9
2022
Statut:
ppublish
Résumé
Tumor-associated macrophages (TAM) are one of the most abundant cell types in many solid tumors and typically exert protumor effects. This has led to an interest in macrophage-depleting agents for cancer therapy, but approaches developed to date have had limited success in clinical trials. Here, we report the development of a strategy for TAM depletion in mouse solid tumor models using chimeric antigen receptor (CAR) T cells targeting the macrophage marker F4/80 (F4.CAR-T). F4.CAR-T cells effectively killed macrophages in vitro and in vivo without toxicity. When injected into mice bearing orthotopic lung tumors, F4.CAR-T cells infiltrated tumor lesions and delayed tumor growth comparably with PD-1 blockade, and significantly extended mouse survival. Antitumor effects were mediated by F4.CAR-T-produced IFNγ, which promoted upregulation of MHC molecules on cancer cells and tumor-infiltrating myeloid cells. Notably, F4.CAR-T promoted expansion of endogenous CD8 T cells specific for tumor-associated antigen and led to immune editing of highly antigenic tumor cell clones. Antitumor impact was also observed in mouse models of ovarian and pancreatic cancer. These studies provide proof of principle to support CAR T-cell targeting of TAMs as a means to enhance antitumor immunity.
Identifiants
pubmed: 36095236
pii: 709883
doi: 10.1158/2326-6066.CIR-21-1075
pmc: PMC10704925
mid: NIHMS1837081
doi:
Substances chimiques
Antigens, Neoplasm
0
Receptors, Chimeric Antigen
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1354-1369Subventions
Organisme : NCI NIH HHS
ID : R01 CA254104
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA257195
Pays : United States
Informations de copyright
©2022 American Association for Cancer Research.
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