PD1 Expression in EGFRvIII-Directed CAR T Cell Infusion Product for Glioblastoma Is Associated with Clinical Response

Front Immunol. 2022 May 6;13:872756. doi: 10.3389/fimmu.2022.872756. eCollection 2022.


The epidermal growth factor receptor variant III (EGFRvIII) has been investigated as a therapeutic target for chimeric antigen receptor (CAR) T cell therapy in glioblastoma. Earlier research demonstrated that phenotypic and genotypic characteristics in T cells and CAR T product predicted therapeutic success in hematologic malignancies, to date no determinants for clinical response in solid tumors have been identified. We analyzed apheresis and infusion products from the first-in-human trial of EGFRvIII-directed CAR T for recurrent glioblastoma (NCT02209376) by flow cytometry. Clinical response was quantified via engraftment in peripheral circulation and progression-free survival (PFS), as determined by the time from CAR T infusion to first radiographic evidence of progression. The CD4+CAR T cell population in patient infusion products demonstrated PD1 expression which positively correlated with AUC engraftment and PFS. On immune checkpoint inhibitor analysis, CTLA-4, TIM3, and LAG3 did not exhibit significant associations with engraftment or PFS. The frequencies of PD1+GZMB+ and PD1+HLA-DR+ CAR T cells in the CD4+ infusion products were directly proportional to AUC and PFS. No significant associations were observed within the apheresis products. In summary, PD1 in CAR T infusion products predicted peripheral engraftment and PFS in recurrent glioblastoma.

Keywords: CAR T cells; GBM; PD-1; glioblastoma; immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ErbB Receptors
  • Glioblastoma* / pathology
  • Humans
  • Neoplasm Recurrence, Local / metabolism
  • Receptors, Chimeric Antigen*
  • T-Lymphocytes


  • Receptors, Chimeric Antigen
  • epidermal growth factor receptor VIII
  • ErbB Receptors

Associated data

  • ClinicalTrials.gov/NCT02209376