Project: Understanding the Immunobiology of Clinical Responses to CD19 CAR T Cell Adoptive Therapy In Lymphoma Patients
Project Leaders: Michael Jensen, M.D. and Stanley Riddell, M.D.
Adoptive therapy with autologous T cells modified to express chimeric antigen receptors (CARs) that target the CD19 molecule expressed on B cell leukemias (CLL and ALL) has shown impressive antitumor activity in small numbers of patients enrolled on early phase clinical trials. Clinical experience to date suggests that lymphomas may be a more challenging tumor to effectively target with CD19-specific CAR T cells. The basis for therapeutic success and failure remains to be elucidated. One of the challenges is that different institutions are using different CAR constructs, cell product compositions, culturing techniques, lymphodepleting conditioning regimens, and patient populations/disease attributes. Consequently, there are no comparisons of key parameters that might predict outcome in lymphoma patients between studies. This project will focus on defining clinical and laboratory parameters that are predictive of efficacy and safety in patients with relapsed/refractory B cell NHL that utilize second generation CD19 CARs and T cell products of defined composition.
The specific aims of this project are as follows:
Aim 1: To quantify CAR T cell engraftment in treated lymphoma patients on COH/FHCRC CD19 CAR T cell trials and correlate engraftment peak magnitude, persistence duration and retention of anti-tumor potency with product composition profile, lymphodepleting preparative regimen used, disease burden at time of adoptive therapy, and anti-tumor efficacy endpoints.
Aim 2: To define the incidence and etiology of cytokine storm/engraftment syndrome in treated lymphoma patients and establish T cell product profile, patient clinical status, and laboratory parameters that are predictive for risk of this toxicity.