期刊
CURRENT OPINION IN PEDIATRICS
卷 26, 期 1, 页码 43-49出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MOP.0000000000000043
关键词
Acute lymphoblastic leukemia; blinatumomab; chimeric antigen receptor; cytokine release syndrome
类别
资金
- National Institutes of Health [R01CA116660]
- Leukemia and Lymphoma Society, Pennsylvania Department of Health, Cookies for Kids Cancer, Solving Kids Cancer
- WW Smith Charitable Trust
- Weinberg Funds
Purpose of reviewRecent clinical trials using T-cell engaging immunotherapies such as bispecific antibodies which target T cells and tumor cells, as well as engineered T cells that express targeting and activation molecules known as chimeric antigen receptors, have demonstrated powerful proof of concept. These therapies result in a significant degree of immune activation in the patient, which has correlated with greatly increased efficacy but also with notable toxicity. These therapies produce nonphysiologic T-cell activation, which is the hallmark of these new, highly active treatments.Recent findingsWe and others have noted cytokine activation profiles that correlate with both toxicity and efficacy in patients receiving T-cell engaging therapies. Effector cytokines such as interferon- are elevated, but so are cytokines that are associated with macrophage activation syndrome/hemophagocytic lymphohistiocytosis, such as interleukin (IL)-10 and IL-6. Although corticosteroids can control some of these toxicities, a targeted approach may produce superior toxicity control without interfering with efficacy. One approach we have developed targets IL-6, a key cytokine in the toxicity response, using the IL-6 receptor antagonist tocilizumab.SummaryDetailed studies of the T-cell activation produced by these novel therapies has led to more targeted approaches that have the potential to control toxicity while maintaining efficacy.
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