Redirecting T cells to treat solid pediatric cancers.
Cancer Metastasis Rev
; 38(4): 611-624, 2019 12.
Article
em En
| MEDLINE
| ID: mdl-31811551
ABSTRACT
The capacity of single-agent therapy with immune checkpoint inhibitors to control solid cancers by unleashing preexisting local antitumor T cell responses has renewed interest in the broader use of T cells as anticancer therapeutics. At the same time, durable responses of refractory B-lineage malignancies to chimeric-receptor engineered T cells illustrate that T cells can be effectively redirected to cancers that lack preexisting tumor antigen-specific T cells, as most typical childhood cancers. This review summarizes strategies by which T cells can be modified to recognize defined antigens, with a focus on chimeric-receptor engineering. We provide an overview of candidate target antigens currently investigated in advanced preclinical and early clinical trials in pediatric malignancies and discuss the prerequisites for an adequate in vivo function of engineered T cells in the microenvironment of solid tumors and intrinsic and extrinsic limitations of current redirected T cell therapies. We further address innovative solutions to recruit therapeutic T cells to tumors, overcome the unreliable and heterogenous expression of most known tumor-associated antigens, and prevent functional inactivation of T cells in the hostile microenvironment of solid childhood tumors.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
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Imunoterapia Adotiva
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Neoplasias
Limite:
Animals
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Child
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Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article