Humanigen Inc (HGENQ)

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Mechanisms of cytokine release syndrome and neurotoxicity of CAR T-cell therapy and associated prevention and management strategies

https://jeccr.biomedcentral.com/articles/10.1186/s13046-021-02148-6

Targeting GM-CSF
GM-CSF is also an important cytokine associated with CAR T-cell-related adverse events, especially ICANS [89, 91]. Lenzilumab, a monoclonal antibody against GM-CSF, can resolve ICANS and CRS induced by CAR T-cells in mouse models by inhibiting myeloid cells and T cells entering the CNS [91]. Intriguingly, instead of dampening CAR T-cell expansion, lenzilumab even enhanced its antitumor effect [91]. The ZUMA-19 trial (NCT04314843) preliminarily showed the efficacy and safety of lenzilumab and Axi-Cel (an FDA-approved CD19 CAR T-cell product) in treating patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL). It was observed that lenzilumab could induce a lower risk of severe CRS and ICANS and reduce inflammatory markers, such as IL-6, CRP, ferritin, MCP-1, IL-8, and IP-10 [168].

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