# Autologous CD19 Targeted 19-28z+ Tcells for the Treatment of Relapsed Diffuse Large B cell Lymphoma in Transplant Ineligible Elderly Patients > **NIH NIH P50** · SLOAN-KETTERING INST CAN RESEARCH · 2020 · $311,063 ## Abstract Despite currently available chemotherapy regimens, patients with relapsed diffuse large B cell lymphoma (DLBCL) ineligible for autologous stem cell transplant (ASCT) have a very poor prognosis and represent an area of unmet need. For this reason, novel approaches are needed for this patient population. One novel approach currently being investigated in the clinical setting is the adoptive transfer of T cells genetically modified to express artificial T cell receptors termed chimeric antigen receptors (CARs) designed to recognize target antigens expressed on the tumor cell surface. To this end, a patient’s own T cells may be isolated and through retroviral or lentiviral gene transfer modified to express the CAR thereby redirecting T cell specificity to the tumor associated antigen. Most B cell malignancies, including most B cell non-Hodgkins lymphomas (NHL), chronic lymphocytic leukemias (CLL) and B cell acute lymphoblastic leukemias (B-ALL) express the B cell specific antigen CD19. Significantly, most DLBCLs similarly express the CD19 antigen. To date we and several other groups have recently reported initial clinical outcomes of patients with both low grade as well as aggressive B cell cancers treated with CAR T cells targeted to the CD19 antigen. To date, these clinical studies have reported anti-tumor responses in patients with low grade B cell CLL and far more markedly in patients with relapsed/refractory B-ALL. More recently, clinical outcomes of a small cohort of patients with relapsed DLBCL treated with CD19 targeted CAR T cells have demonstrated promising but suboptimal responses, with 4 of 7 patients demonstrating complete remissions (CRs) but only 3 of 4 responses being relatively durable (9-22 months) with relatively short follow-up. An additional and relevant immune-based approach to cancer therapy, having only recently demonstrated moderate clinical benefit in the setting of DLBCL after autologous bone marrow stem cell transplantation, is immune-checkpoint blockade through infusion of antagonistic MAb’s targeted to the T cell PD-1 receptor, which when engaged to either the PD-L1 or PD-L2 ligand induces T cell anergy. As a result, blockade of this T cell checkpoint pathway with PD-1 specific MAbs may in turn enhance the anti-tumor function of tumor targeted T cells and may further modulate an otherwise immune suppressive tumor microenvironment to one more suitable for immune targeted tumor eradication by both CAR T cells as well as recruited endogenous anti-tumor immune effectors. The primary goal of this project is to optimize CD19 targeted CAR T cell therapy in patients with DLBCL. To this end in Aim 1 we will initially apply our CD19 targeted 19-28z CAR T cell approach to very poor prognosis elderly relapsed/refractory ASCT ineligible DLBCL patients, a condition representing an unmet medical need, in a phase I/II clinical trial as a single agent therapy following salvage chemotherapy. In Aim 2 we utilize a clinically relevant immun... ## Key facts - **NIH application ID:** 9988855 - **Project number:** 5P50CA192937-05 - **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH - **Principal Investigator:** Renier Joseph Brentjens - **Activity code:** P50 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2020 - **Award amount:** $311,063 - **Award type:** 5 - **Project period:** 2016-08-30 → 2022-07-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/9988855 ## Citation > US National Institutes of Health, RePORTER application 9988855, Autologous CD19 Targeted 19-28z+ Tcells for the Treatment of Relapsed Diffuse Large B cell Lymphoma in Transplant Ineligible Elderly Patients (5P50CA192937-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9988855. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*