Research we fund

We are conducting a clinical trial testing a novel form of immunotherapy, called a bispecific antibody, as part of initial treatment for patients with follicular lymphoma. The goal of the trial is two-fold: 1) to establish a highly effective, chemotherapy-free treatment option for patients with follicular lymphoma, and 2) to establish predictors of response and toxicity that can guide treatment decisions for future patients with follicular lymphoma.

Vitamin A is safe, well tolerated and positively affects gut immune health. Graft versus host disease (GVHD) is a life-threatening complication of bone marrow transplant (BMT) which happens due to inflammatory changes in the gut. We harnessed the anti-inflammatory properties of vitamin A by giving it to children before bone marrow transplant (BMT) and showed reduction in acute gut and moderate/severe chronic GVHD. We will validate our findings in this currently proposed study of an independent group of adult BMT patients. We will give vitamin A or placebo before BMT to adult BMT patients and observe for reduction of chronic GVHD in vitamin A recipients compared to placebo. This study will be a step forward in adoption of vitamin A as a universal strategy to prevent GVHD which is affordable ($1.25 for entire treatment), non-toxic, and doesn’t suppress the immune system.

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.

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.

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.

Leukemia recurrence remains the most common type of treatment failure after allogeneic hematopoietic cell transplant for children and young adults with high-risk acute myelogenous leukemia (AML), occurring in 40-50% of patients. Novel treatment strategies are needed to attain durable remissions and provide long-term cure. We have developed a novel memory-like (ML) NK cell immunotherapy that has demonstrated potent activity against AML in preclinical and early clinical studies. We propose a new clinical trial combining donor-derived ML NK cells adoptive cellular therapy with modified αβT cell-depleted haploidentical HCT to enhance graft-versus-leukemia and reduce relapse in pediatric and young adult patients with high-risk AML.

T-acute lymphoblastic leukemia (T-ALL) is an aggressive leukemia with limited treatment options after first-line chemotherapy. Our preclinical work in animal models of T-ALL demonstrated the activity of a novel-novel combination treatment strategy, which includes LP-118 (activator of suicide pathways within leukemic cells) and tyrosine kinase inhibitors (inhibiting growth-promoting LCK and ACK1 signaling pathways). Leveraging the mechanistic insights gained from our laboratory work, we propose a phase Ib/II study investigating the feasibility and efficacy of the combined LP-118, ponatinib, and salvage chemotherapy in patients with relapsed T-ALL. This precision medicine approach addresses an unmet need in a fatal disease which lacks effective therapies.

In up to half of patients with hematologic malignancies undergoing allogeneic stem cell transplantation, the trajectory of a smooth recovery toward cure is disrupted by acute graft-versus-host disease (aGVHD). Inspired by the role of intestinal microbial communities in aGVHD pathogenesis, we recently completed the largest fecal microbiota transplantation (FMT) trial to date in transplant recipients. We established the safety of standardized third-party FMT and characterized FMT effects on the microbiota, leading to the proposed randomized, placebo-controlled phase 2 trial of FMT to prevent aGVHD.

CD19 targeting chimeric antigen receptor (CAR) T cell therapies (CAR19) are effective treatments for patients with non-Hodgkin Lymphoma (NHL), however, the majority of these patients will relapse. We have now evaluated a CD22 targeting CAR T cell therapy (CAR22) in patients who have large B cell lymphoma who have relapsed after CAR19 therapy and found that this therapy is both safe and effective resulting in a high rate of durable complete responses. We will now test this promising CAR22 for the first time in patients with other non-Hodgkin Lymphoma subtypes including mantle cell lymphoma, follicular lymphoma, and other CD22-expressing lymphomas.