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Redirecting T cells to treat solid pediatric cancers.
Rauwolf, Kerstin K; Rossig, Claudia.
Afiliação
  • Rauwolf KK; Department of Pediatric Hematology and Oncology Albert-Schweitzer Campus 1, University Children's Hospital Muenster, 48149, Münster, Germany.
  • Rossig C; Department of Pediatric Hematology and Oncology Albert-Schweitzer Campus 1, University Children's Hospital Muenster, 48149, Münster, Germany. rossig@uni-muenster.de.
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfócitos T / Imunoterapia Adotiva / Neoplasias Limite: Animals / Child / Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfócitos T / Imunoterapia Adotiva / Neoplasias Limite: Animals / Child / Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article