CD72 Nano-CARs for the Treatment of MLLr B-Cell Acute Lymphoblastic Leukemia
Abstract
B-cell acute lymphoblastic leukemia, commonly known as B-ALL, is the most common cancer diagnosed in Americans under the age of 40. Together, individuals of this age are known as pediatric, adolescent, and young adults. Our proposal here specifically addresses cancers in this Peer Review Cancer Research Program Fiscal Year 2021 Topic Area. Our goal under the proposed research is to develop a new type of treatment for these patients. In many ways, treatment of young patients with B-ALL is one of the great success stories in our society’s battle with cancer. With current treatments based on chemotherapy, cure rates for young B-ALL patients appear to exceed 85%. This result is truly remarkable when compared to other cancers in children and adults. However, it is important to note that despite this overall success, the 10%-15% of B-ALL patients who are not cured still amount to hundreds of young lives lost every year to this cancer. In addition, there are approximately 10% of pediatric B-ALL patients, including the large majority of babies under the age of 24 months, who carry a specific alteration in the genome of their tumor cells called MLLr. These patients only have cure rates of approximately 40%. Can we do better for these patients currently left behind? Rationale: In the past several years, we have had an incredibly important advance for patients who fail at least two different types of therapy. This advance is called CAR-T cells, which involve taking a patient’s own blood cells, reprogramming them to attack their tumor, and re-introducing these reprogrammed blood cells into the body. CAR-T cells attacking a protein called CD19, which is present on the surface of B-ALL tumor cells, have been a huge breakthrough. These CD19-targeting CAR-T cells, with a single treatment, have been able to cure about 50% of these patients who failed other treatments. These patients previously only had about 10% long-term survival. However, even in the era of these impressive CD19 CAR-T therapies, 50% of young B-ALL patients still do not achieve cures after this treatment. What can we do for them? Our proposal here addresses the questions above. In recently-published work, we have discovered a different target, called CD72, that is highly expressed on MLLr B-ALL tumor cells. CD72 is also present on all other B-ALL patient samples that we have tested. We believe finding this new target is important, as it could provide another option to attack tumors in patients who do not respond to CD19-directed treatment. Or, potentially, targeting CD72 may work better than targeting CD19 in MLLr B-ALL patients. To target CD72, we went on to develop a new type of CAR-T cell that attacks the tumor cell. These new CAR-T’s recognize the tumor cell using a binding element called synthetic nanobody. No one had previously used this approach to develop a CAR-T cell and we believe that it may have great promise for cancer treatment. In particular, we believe that our therapy may have strong advantages over other CAR-T cells that have been investigated to treat patients failing CD19-targeted therapy, but which do not appear to lead to cures. Given the novelty of our strategy, we aim to address the Overarching Challenge of transforming cancer treatment through the identification of new targets for recurrent disease and improving immunotherapy. Furthermore, successful development of this new type of CAR-T cell here may accelerate the development of similar immune cell treatments for other diseases. Goals and Objectives: We have made significant progress in demonstrating that our cellular therapy, which we call CD72 nanoCAR-T, works very well in destroying B-ALL tumor cells in the laboratory. Our next major goal is to perform essential steps needed to move CD72 nanoCAR-Ts closer to treating patients. Achieving the milestones necessary to present our CD72 nanoCAR-T’s to the U.S. Food and Drug Administration (FDA) and o
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210807
Entities
People
- Arun Wiita
Organizations
- United States Army
- University of California, San Francisco