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11-08-2017 | Glioblastoma multiforme | Article

Advisory board expert summary

Michael Weller MD

Summary of: A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma

Chimeric antigen receptor (CAR) T cells are one of the most interesting developments in immunotherapy for cancer in the last decade. Yet, as for other immunotherapies, tolerability, safety, and efficacy greatly depend on the specificity with which a certain antigen can be targeted.

In that regard, the vIII mutation of epidermal growth factor receptor (EGFRvIIII) has been considered to be particularly promising in glioblastoma because approximately 25% of glioblastomas carry this mutation which should not be expressed in any normal human cell.

In this Science Translational Medicine study, O’Rourke and colleagues report the initial experience with 10 patients with recurrent glioblastoma who were treated with CAR-T EGFRvIII cells. One patient experienced prolonged stable disease and there was immunological proof of concept in that CAR-T EGFRvIII trafficking to the tumor site could be demonstrated.

Neuroimaging changes after CAR-T immunotherapy remained challenging to interpret as seen for other approaches of immunotherapy.

There was evidence of counteracting immunosuppressive processes in the tumor microenvironment in response to CAR-T infusion, indicating that systemic or local efforts at overcoming immunosuppression might be required to confirm the efficacy of CAR T cell approaches in glioblastoma.

Related news story: Mutation-directed CAR T cell therapy feasible in recurrent glioblastoma

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