Research We Fund

Most CLL patients treated with CAR T-cells that target the CD19 antigen on the cell do not achieve a complete remission. CLL cells express other molecules on their surface; one of them is the receptor for BAFF (BAFF-R), which is highly expressed. We propose a phase I trial investigating LMY-920 for treatment of CLL. LMY-920 is a different type of CAR T-cell because it does not rely on an antibody structure to identify BAFF-R, but uses the structure of the ligand BAFF itself, and this may help avoid resistance to CAR T-cells.

We also aim to improve the quality of the CAR T-cell product by removing the circulating B cells with a monoclonal antibody prior to collecting lymphocytes for manufacture.

This Specialized Center of Research is focused on identifying the contributions of chromosome 21, which is present in three copies in individuals with Down syndrome (DS), to acute leukemia. Children with DS are at a 20-fold increased risk of leukemia compared to the overall pediatric population and frequently have other health issues that complicate leukemia treatment. Although acute myeloid leukemia in children with DS (ML-DS), which frequently evolves from transient abnormal myelopoiesis (TAM), has a better outcome than acute myeloid leukemia (AML) in children without DS, those who relapse following treatment face an extremely poor prognosis. Similarly, children with DS who develop B-ALL have a worse prognosis than those without DS due to excessive treatment-related mortality and increased risk of relapse. Our overarching, united goal is to develop novel therapies to cure DSassociated leukemias and to reduce the side effects of treatment in this vulnerable population. In addition to children with DS, our study has major implications in other cases of pediatric and adult leukemias. For example, chromosome 21 amplification is one of the most significant gains in several classes of malignancies, including certain subtypes of AML, hyperdiploid ALL, and iAMP21. Amplification of chromosome 21 is also a feature of the acute leukemia phase of a disease named myelofibrosis. Therefore, insights we gain from this research will impact a large group of patients with acute leukemia.

Although many patients with diffuse large B-cell lymphoma (DLBCL) are cured with standard therapy, others will die from their disease. Survival is significantly worse for African American (AA) patients and those with Epstein- Barr virus (EBV), which is common in patients from Latin America. The reasons behind these poor outcomes are not well understood, in part because most studies of molecular features in lymphomas have not included enough patients from these racial and ethnic groups.

Lymphoma tumors include not just the cancer cells themselves, but also surrounding cells and proteins that help the cancer cells survive. To understand why AA DLBCL patients and those with EBV have worse outcomes, we will look at differences in genes and tumor make-up in a large collection of DLBCL samples with good representation of these patient groups. Our goal is to find the factors most important to target with new treatments to improve survival for AA and EBV+ patients. We will also build innovative models of DLBCL in the lab to (1) discover how tumor make-up and gene changes affect tumors’ response to treatment, and (2) test new therapies designed to benefit AA DLBCL patients and patients with EBV-associated DLBCL.

Overall, our LLS SCOR Program seeks to bridge the knowledge gap in molecular features of DLBCL in underrepresented populations, and fast-track development of novel targeted therapies that can improve outcomes for these vulnerable patients.

In December 2024, LLS made an equity investment in Solu Therapeutics to "Support Preclinical and Clinical Development of STX-0712 in hematological malignancies, primarily in CMML."

Solu Therapeutics is a biotechnology company dedicated to developing next-generation therapeutics to eliminate disease-driving cells in cancer, immunology and other therapeutic areas. The company’s proprietary CyTAC (Cytotoxicity Targeting Chimera) and TicTAC (Therapeutic Index Control Targeting Chimera) platforms enable the development of innovative medicines that combine the target-binding capability of small molecules with the therapeutic power of biologics.

STX-0712 is a CyTAC targeting the GPCR CCR2, which is a selective marker expressed at high levels on pathogenic monocytes. Pathogenic monocytes expressing CCR2 have been shown to be the key drivers in some hematological malignancies. A Phase 1 trial is ongoing to assess the safety and efficacy of STX-0712 in patients with advanced CMML (NCT06950034).