Disease relapse is a leading etiology of morbidity and mortality for patients with non-Hodgkin lymphoma (NHL) and autologous hematopoietic stem cell transplant following a myeloablative preparative regimen (auto-HSCT) can salvage only a subset of these patients. This Lymphoma SPORE Project seeks to develop targeted cellular immunotherapy capable of eradicating lymphoma post-transplant minimal residual disease using CD19-specific T cell adoptive immunotherapy AIT. During the last funding cycle, we have developed a genetic engineering approach to equip T cells with the ability to recognize and lyse tumor cells of B-cell lineage NHL using chimeric antigen receptors (CARs) specific for CD19 and initiated three clinical trials to test successive modifications of this therapy.
The Specific Aims of this project are as follows:
Aim 1: To determine if CD19R-CAR+ TE(CM) can be routinely isolated from NHL patients and, if after ex vivo propagation at clinical scale, they execute CD19-specific anti-lymphoma effector function and retain engraftment fitness (Testing pre-clinical trial).
Aim 2: To examine the feasibility of manufacturing and the safety of infusing escalating doses of CD19R-CAR+ TE(CM) to patients with recurrent B-cell NHL in conjunction with auto-HSCT (Human Clinical Trials).
Aim 3: To evaluate the duration and magnitude of persistence, memory niche repopulation, and anti-CD19 effector function of adoptively transferred CD19R-CAR+CD8+ TE(CM) in an expanded Phase I/II cohort of NHL patients treated both at City of Hope and Fred Hutchinson Cancer Research Center (Examine the effectiveness of the therapy).