Defining Optimal T-Cell Characteristics for Pediatric Chimeric Antigen Receptor (CAR) T-cell Trials

Julie Rivers | 2017

Advisor: Christopher I-Fu Li

Research Area(s): Cancer Epidemiology, Clinical Epidemiology



Engineered chimeric antigen receptor (CAR) T cells have emerged as a powerful, highly personalized immunotherapy in pediatric cancer. Early phase clinical trials using CAR T cells targeting CD19 have resulted in complete response (CR) rates as high as 93% in children with relapsed and refractory acute lymphoblastic leukemia (ALL). Despite this success, there are many challenges that must be overcome before CAR T cell therapy can be used routinely in pediatric ALL or other malignancies.


To develop novel biomarkers that will identify patients at high risk for poor product expansion, treatment failure and/or toxicity with current immunotherapy protocols and that may ultimately help improve manufacturing methods to produce safer and more effective CAR T cells.


Using flow cytometry, we evaluated T cell characteristics (memory phenotype, cytokine production, presence of markers of activation/exhaustion) of starting products in 43 patients enrolled and treated in a Phase I clinical trial, PLAT-02. Potential predictors of poor product expansion were assessed using the Wilcoxon Rank Sum Test.


A higher percentage of cells producing cytokines and expressing PD-1 in CD4 starting products was associated with poor expansion. Poor expansion was not associated with patient toxicities or outcomes. Discussion: Increased cytokine production and PD-1 expression suggest a more differentiated, effector-like phenotype of starting products that subsequently experience poor expansion, consistent with preclinical data, although numbers are limited.


Ongoing correlative biology studies will be important in future immunotherapy trials as we seek to identify biomarkers that predict product expansion, toxicities and outcomes.