WP5 Follow-up of EURE-CART Phase I/IIa and correlative studies
Objectives of WP5
- To measure the kinetics and the in vivo functional phenotype of EURE-CART cells.
- To evaluate and manage potential late toxicities.
- To demonstrate anti-tumour efficacy.
The main project tasks are the following
All patients receiving EURE-CART cells will be monitored for the clinical outcome according to standard disease-specific criteria and for detecting MRD.
The analysis of EURE-CART clinical results will be analysed over-time to proceed on dose escalation foreseen in the study design. Moreover, a time window of 3 months has been allocated for analysis of Phase I results and preparation of an interim report for advice on how to proceed to Phase IIa and, in particular, for recommendations on the inclusion of paediatric patients.
The engraftment and the persistence of EURE-CART cells (pharmacokinetics) will be measured overtime at least until day+180 after infusion. The infused cells able to persist in vivo after infusion will be characterized for their sub-populations (including, CD8, CD4, naïve, stem memory, central memory, effector memory or terminally differentiated, and Treg) and functional polarization (according to Th1/Th2/Th17 cytokine profile). Moreover, patient’ plasma will be monitored for cytokine level using a multiplex approach, to investigate correlation with patient outcome, T cell persistence and/or toxicity occurrence. In case of oligoclonal/ clonal T cell expansion, integration sites of the transgene will be evaluated.
Important correlative studies will be performed by WP5, including the evaluation on how EURE-CART cells impact on patient’s immune system and cross-priming of naturally occurring tumour-specific CTLs as well as to define several product features correlating to clinical response.