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Toxicity management for patients receiving novel T-cell engaging therapies

2013; Lippincott Williams & Wilkins; Volume: 26; Issue: 1 Linguagem: Inglês

10.1097/mop.0000000000000043

1531-698X

David M. Barrett, David T. Teachey, Stephan A. Grupp,

Autoimmune and Inflammatory Disorders Research

Purpose of review Recent 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 findings We 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-γ 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. Summary Detailed 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.