Pan-heme CAR: Anti-CD38 CAR T cells for myeloid, lymphoid and plasma cell malignancies
Carl June
MDThe Trustees of the University of Pennsylvania, Medical Center
Project Term: October 1, 2019 - May 31, 2025
Our SCOR team has a razor-sharp focus on an exciting new treatment modality for blood cancers: chimeric antigen receptor (CAR) T cells. T cells can be trained to target cancer cells by genetic modification. In fact, previous support from the Leukemia & Lymphoma Society allowed us to successfully develop CAR T cells targeted to CD19, a pan-B cell marker. This treatment, generically called CART-19, was approved by the FDA in 2017 for the treatment of B-cell acute lymphoid leukemia (B-ALL) and in 2018 for some non-Hodgkin lymphoma (NHL), with promising results in other B cell malignancies such as chronic lymphocytic leukemia (CLL). Thus, the development of a single therapy for a single disease (initially, CLL) paid handsome dividends when translated to a broader range of CD19-expressing malignancies (ALL, NHL).
The goal of our new project is to build upon this model with a comprehensive program to develop CAR T cells that have the potential to be even more broadly applicable to a variety of hematologic malignancies, including acute myeloid leukemia (AML), T-cell ALL, and multiple myeloma.
This time, the molecule of interest is CD38. Unlike CD19 it is not restricted just to B cells. We think CD38 may be particularly relevant because it has several biological functions with a role in cancer cells’ evasion of the immune system. By focusing on CD38 we plan to develop a new treatment for cancer, as well as to devote significant resources to understanding what this relatively under-studied molecule does in cancer cells and in normal cells. We then aim to treat a small number of children and adults suffering from leukemia or myeloma with anti-CD38 CAR T cells. We hope that by the time of its completion, support of this project by the LLS will have generated another innovative treatment for patients with a variety of blood cancers. In order to accomplish our goals, we have assembled a multidisciplinary team of scientists and physicians, most of whom have worked together before to develop CART cell therapy for B-cell disease. The main components of the program are: 1. CART cells for adult AML. 2. CART cells for pediatric AML. 3. CART cells for T-ALL. 4. CART cells for multiple myeloma.
The group has extensive experience at bringing novel cellular therapies to patients with hematologic malignancies.