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Toxicity management for patients receiving novel T-cell engaging therapies.

ABSTRACT: 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.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-? 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.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.

SUBMITTER: Barrett DM

PROVIDER: S-EPMC4198063 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Toxicity management for patients receiving novel T-cell engaging therapies.

Barrett David M DM Teachey David T DT Grupp Stephan A SA

Current opinion in pediatrics 20140201 1

<h4>Purpose of review</h4>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 ...[more]

PMID: 24362408

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Toxicity management for patients receiving novel T-cell engaging therapies.

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Toxicity management for patients receiving novel T-cell engaging therapies.

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