期刊
BRITISH JOURNAL OF HAEMATOLOGY
卷 169, 期 4, 页码 463-478出版社
WILEY
DOI: 10.1111/bjh.13340
关键词
T lymphocytes; immunotherapy; gene transfer; cellular therapies
类别
资金
- Great Ormond Street Hospital Childrens Charity [W0911] Funding Source: researchfish
- National Institute for Health Research [NIHR-RP-R3-12-001] Funding Source: researchfish
- Department of Health [NIHR-RP-R3-12-001] Funding Source: Medline
- National Institutes of Health Research (NIHR) [NIHR-RP-R3-12-001] Funding Source: National Institutes of Health Research (NIHR)
T cells can be redirected to recognize tumour antigens by genetic modification to express a chimeric antigen receptor (CAR). These consist of antibody-derived antigen-binding regions linked to T cell signalling elements. CD19 is an ideal target because it is expressed on most B cell malignancies as well as normal B cells but not on other cell types, restricting any on target, off tumour' toxicity to B cell depletion. Recent clinical studies involving CD19 CAR-directed T cells have shown unprecedented responses in a range of B cell malignancies, even in patients with chemorefractory relapse. Durable responses have been achieved, although the persistence of modified T cells may be limited. This therapy is not without toxicity, however. Cytokine release syndrome and neurotoxicity appear to be frequent but are treatable and reversible. CAR T cell therapy holds the promise of a tailored cellular therapy, which can form memory and be adapted to the tumour microenvironment. This review will provide a perspective on the currently available data, as well as on future developments in the field.
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