Журнал цитокиновой биологии

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Cytokine Release Syndrome (CRS) Reporting and Mechanism in Immuno-Oncology Clinical Trials

Thibault Isaacs

Allogeneic hematopoietic cell transplantation using HLA haploidentical donors and post-transplantation The benefits of cyclophosphamide (PT/Cy-haplo), including its inexpensive cost, high likelihood of finding a compatible donor, and quick availability of donors, make it a widely utilised drug. In patients receiving PT/Cy-haplo, particularly when peripheral blood is used, cytokine release syndrome (CRS), caused by bidirectional alloreaction between host and donor, frequently occurs. The immunosuppressive humanised monoclonal antibody CAMPATH 1-H, which recognises CD52 on lymphocytes and monocytes, is clinically linked to a first-dose cytokine-release syndrome involving TNFa, IFNg, and IL-6. Since cytokine release is isotype dependent, in vitro models have been used to identify the cellular source and mechanism responsible for it. Rat IgG2b and human IgG1 isotypes induce the highest levels of cytokine release, which is inhibited by an antibody to CD16, the low affinity Fcreceptor for IgG(FcgR).