English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

BACKGROUND A therapeutic approach for chimeric antigen receptor T (CART) cell therapy in glioblastoma is targeting the epidermal growth factor receptor variant III (EGFRvIII), present in approximately 30% of glioblastomas. While earlier research demonstrated that phenotypic and genotypic characteristics in patient T cells and CART product may predict therapeutic success for hematologic malignancies, no study has investigated such determinants for clinical response in glioblastoma. METHODS We analyzed apheresis and infusion products for patients in the first-in-human trial of EGFRvIII-directed CART for recurrent glioblastoma (NCT02209376, n=9). Inherent T cell phenotypes were characterized by flow cytometry assay using a panel of 27 markers. Clinical response was quantified via engraftment in peripheral circulation and time-on-trial (ToT). RESULTS Mean area under the curve (AUC) peripheral CART engraftment for the study period was 213 log10 copies/μg (SD=173) and mean ToT was 134 days (SD=173). For the CAR+/CD4+ population in the infusion product, PD1 positivity was positively associated with AUC engraftment (r=0.753, P=0.012) and ToT (r=0.800, P=0.010). On immune checkpoint inhibitor analysis, CTLA-4, TIM3, and LAG3 did not exhibit significant associations with AUC engraftment or ToT. For activation markers, PD1/GRZB (r=0.794, P=0.011) and PD1/HLA-DR (r=0.769, P=0.016) were directly associated with ToT. PD1/GRZB was also predictive of AUC engraftment (r=0.794, P=0.011). For the CAR+/CD8+ population, PD1 positivity correlated with elevated AUC engraftment (r=0.639, P=0.047). In the CAR-/CD4+ population, PD1 remained positively correlated with AUC engraftment (r=0.690, P=0.027) and ToT (r=0.726, P=0.027). No significant associations were observed for apheresis products. CONCLUSION PD1 in CART infusion products predicted peripheral engraftment and ToT in recurrent glioblastoma. Double-positive cells for PD1 and activation markers also displayed a positive correlation, suggesting PD1 highlights a population of activated CAR T cells. Further characterization of predictors of EGFRvIII-directed CART treatment efficacy may improve selection of patients and starting T cell populations for clinical expansion.

IMMU-16. CHARACTERISTICS OF EGFRVIII-DIRECTED CART CELL INFUSION PRODUCT ASSOCIATED WITH CLINICAL RESPONSE IN RECURRENT GLIOBLASTOMA