Research we fund

Posttransplant lymphoproliferative disorders (PTLD) are a group of lymphomas that arise during immunosuppression following organ transplantation and are a significant source of morbidity and mortality. PTLD remains challenging to treat due to disease heterogeneity, patient comorbidities, the risk of infectious complications, and organ rejection. The goals of this proposal are to (1) study the therapeutic efficacy and safety of dose modified R-EPOCH in High-Risk PTLD patients; (2) determine the utility of ctDNA defined molecular response as a novel risk-stratification biomarker in PTLD; (3) understand the impact of immune-suppression on T cell function, T cell receptor diversity, and the detection of oncoviruses. The overall goal is to reduce morbidity and identify novel biomarkers for personalized precision treatment decisions to improve survival in this devastating disease.

Project Term: February 1, 2025 - January 31, 2028

We will conduct a decentralized randomized controlled trial of a high-fiber plant-based dietary intervention among patients with multiple myeloma undergoing induction chemoimmunotherapy. The study will assess whether the intervention (meals and virtual coaching) leads to improved rates of complete response, and quality of life mediated by improvements in weight and insulin resistance. The study is expected to provide rigorous evidence of the effectiveness of this intervention in patients with newly diagnosed multiple myeloma and support the development of low-cost, minimal-risk nutrition as a strategy to improve cancer treatment outcomes.

Project Term: March 1, 2025 - February 29, 2028

T-cell leukemias and lymphomas have devastating outcomes if they recur after or don’t respond to standard treatment, with the only hope of cure being bone marrow transplant (BMT). Unfortunately, many pediatric, adolescent and young adult (AYA) patients are unable to achieve clinical remission (and thus unable to proceed to BMT) with standard salvage therapies, which are often even more toxic than upfront therapies. Available treatment options for patients with relapsed or refractory T-cell malignancies (particularly pediatric and AYA patients) are lacking, thus 3-year survival rates are <15% for these patients. This proposal aims to study a less toxic, targeted approach using patient or donor-derived T-cells engineered to target an antigen expressed on over 90% of T-cell malignancies that affect pediatric and AYA patients (CD7 Chimeric Antigen Receptor T-cells).

Project Term: July 1, 2024 - June 30, 2027

Our recent studies have identified specific bacteria that can potentially promote the growth of human myeloma tumor cells. We are now testing if eradicating these bacteria in MGUS patients will be effective for prevention of myeloma.

Project Term: July 1, 2023 - June 30, 2026

Bispecific antibodies are a new, highly effective immunotherapy for multiple myeloma. Most bispecific antibody therapies have been tested as continuous therapies in which patients continue receiving the treatment until the myeloma starts growing again. Preliminary results suggest that patients with good responses may be able to stop therapy and enjoy a period of time off-therapy with close observation, which may limit long term toxicities caused by continuous therapy. We propose a clinical trial to test this limited-duration approach with recently approved bispecific antibodies for multiple myeloma.

Project Term: February 7, 2024 - June 30, 2027

Angioimmunoblastic T-cell lymphoma is a rare, aggressive form of T-cell lymphoma associated with poor clinical outcomes in response to current therapeutic approaches. Recurrent oncogenic mutations in isocitrate dehydrogenase 2 (IDH2) have been identified in patients with angioimmunoblastic T-cell lymphoma and this represents a targetable lesion in other malignancies. However, comprehensive investigations of mutant IDH2 inhibition in angioimmunoblastic T-cell lymphoma are lacking, and this may represent a new therapeutic avenue for a patient population in need of newer treatments

Project Term: July 2, 2023 - June 30, 2026

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.

Project Term: July 1, 2024 - June 30, 2027

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.

Project Term: October 1, 2024 - September 30, 2027

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.

Project Term: July 1, 2024 - June 30, 2027

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.

Project Term: July 1, 2024 - June 30, 2027

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.

Project Term: July 1, 2024 - June 30, 2027

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.

Project Term: July 1, 2023 - June 30, 2026