Research we fund

Black and Hispanic individuals diagnosed with Hodgkin lymphoma (HL) face worse survival rates across all ages. Using an innovative data source, this study will examine differences by insurance status in the receipt and quality of HL treatment in Aim 1 and care engagement and support after treatment (survivorship care) in Aim 2. Using diverse patient voices, this study will characterize and understand how patients make decisions about treatment and survivorship care by insurance type in Aim 3.

Cytotoxic cells of the immune system, including T and NK cells, can be targeted to seek out and destroy leukemia, lymphoma and myeloma cells by engineering them to express chimeric antigen receptors (CARs) which empower the cell to home to and kill the cancer cells. Typically, such CAR-T and CAR-NK cells are generated from a patient's own blood, but sometimes heavy pre-treatment with chemotherapy leaves inadequate supplies of T and NK cells. We propose to generate T and NK cells from Pluripotent Stem Cells, which through genetic manipulation can be rendered suitable for treating any patient with an "off-the-shelf" cell product, hence facilitating otherwise cumbersome, labor-intensive, and expensive patient-specific cell therapies.

Relapse in patients with acute myeloid leukemia (AML) after hematopoietic cell transplant (HCT) is associated with extremely poor prognosis and thus remains a major unmet need. Natural killer (NK) cells are attractive for treating relapse in the post-HCT setting as these cells are not associated with causing graft-versus-host-disease. Cytokine-induced memory-like (CIML or memory-like) NK cells described by our group, demonstrate enhanced anti-leukemia activity, and persist for up to several months in an immune compatible post HCT setting (when derived from the stem cell donor). The goal of this trial is to evaluate donor CIML NK cells early after HCT in AML patients with measurable residual disease (MRD) and therefore otherwise with a high risk of relapse.

This team science program from Washington University will develop new immunotherapy treatments for patients with hard to treat or incurable lymphomas. The team includes physicians and scientists who have developed new ideas in the laboratory for immune-based treatment, and will translate these to clinical trial testing. These include engineered natural kill cells, healthy donors T cell engineered to attack a T cell lymphoma, and lymphoma-patient specific mutations as vaccine targets.

Venetoclax-based regimens are the standard of care for many patients with acute myeloid leukemia (AML) and are highly active therapeutic strategies for this challenging disease. However, some patients do not respond, and most patients who do respond will relapse. We have discovered that resistance to venetoclax may be mediated by the movement patterns of calcium throughout a cell. Furthermore, we have found that mitoxantrone, a conventional chemotherapy agent, can interrupt these calcium fluctuations at very low doses. Therefore we have proposed a clinical trial using lower-dose mitoxantrone for AML patients whose disease has resistance to venetoclax-based regimens.

In November 2022, LLS made an equity investment in Dren Bio to "Support Clinical Development of the DR-01 Program for Rare Leukemia & Lymphoma Indications Including Large Granular Lymphocyte Leukemia (LGLL) and Cytotoxic Lymphomas."

Dren Bio is a clinical-stage biopharmaceutical company focused on developing therapeutic antibodies for the treatment of cancer, autoimmune and other serious diseases. Dren Bio’s pipeline encompasses two distinct programs, the first focusing on the engineering of antibodies with enhanced antibody-dependent cellular cytotoxicity (ADCC) capabilities and the second revolving around its proprietary Targeted Myeloid Engager and Phagocytosis Platform.

DR-01 is a novel antibody targeting CD94 which is known to be upregulated on LGLL cells. DR-01 functions through depletion of target cells via ADCC by means of fratricide, a method in which the same cell type induces ADCC on each other. A Phase 1/2 trial is ongoing to assess the safety and efficacy of DR-01 in previously treated LGLL patients and cytotoxic lymphomas (NCT05475925).

DR-0201 is a first-in-class bispecific antibody capable of engaging tissue-resident and trafficking myeloid cells to induce deep B cell depletion via targeted phagocytosis. DR-0201 is currently being evaluated in a Phase 1 study in B-NHL patients (NCT06392477).

In August 2017, TAP partnered with Ryvu Therapeutics (formerly known as Selvita) to support "A Phase 1b Study of SEL120 in Patients With Acute Myeloid Leukemia or High-risk Myelodysplastic Syndrome."

Ryvu Therapeutics is a clinical-stage drug discovery and development company focusing on novel small molecule therapies that address emerging targets in oncology using a proprietary discovery engine platform.

RVU120 (SEL120) is a highly selective first-in-class CDK8/CDK19 small molecule inhibitor. Ryvu is currently enrolling several Phase 2 clinical trials: RVU120 in combination with venetoclax for patients with relapsed/refractory AML (RIVER-81, NCT06191263), RVU120 as monotherapy for patients with low-risk myelodysplastic syndromes (REMARK, NCT06243458) and RVU120 as monotherapy and in combination with ruxolitinib for patients with myelofibrosis (POTAMI-61, NCT06397313).

In August 2017, TAP partnered with Ryvu Therapeutics (formerly known as Selvita) to support "A Phase 1b Study of SEL120 in Patients With Acute Myeloid Leukemia or High-risk Myelodysplastic Syndrome."

Ryvu Therapeutics is a clinical-stage drug discovery and development company focusing on novel small molecule therapies that address emerging targets in oncology using a proprietary discovery engine platform.

RVU120 (SEL120) is a highly selective first-in-class CDK8/CDK19 small molecule inhibitor. Ryvu is currently enrolling several Phase 2 clinical trials: RVU120 in combination with venetoclax for patients with relapsed/refractory AML (RIVER-81, NCT06191263), RVU120 as monotherapy for patients with low-risk myelodysplastic syndromes (REMARK, NCT06243458) and RVU120 as monotherapy and in combination with ruxolitinib for patients with myelofibrosis (POTAMI-61, NCT06397313).

The field of cancer treatment has made remarkable progress with the adoption of targeted therapy; however, small molecule drugs have limitations such as drug resistance and off-target toxicities. To overcome these challenges, we have developed an innovative approach that enhances the potency and precision of small molecule drugs. Our cutting-edge high-precision pretargeted nanoparticles can deliver potent triple inhibitors that effectively combat drug-resistant mantle cell lymphoma and dual proteolysis targeting chimeras (PROTACs) for treatment of transformed follicular lymphoma. Our proposal is supported by extensive preliminary data, and we are excited to be at the forefront of this revolutionary novel treatment strategy.

The goal of our laboratory is to discover, study, and the translate new leukemia therapies to the clinic. In this project, we are studying a signaling pathway, called PI3 kinase gamma, that we believe is important in patients with AML and might lead to new treatments using drugs that target its activity.