Research we fund

We discovered mesothelin to be expressed on AML cells, but absent on normal cells, thus providing a unique target to eliminate leukemia without causing cytopenia. We demonstrated efficacy of mesothelin-directed immunotherapy (CART) in AML. In collaboration with Eureka pharmaceutical, we will conduct the first trial using a mesothelin-directed CART in childhood AML.

This proposal examines the use of CD19-directed chimeric antigen receptor (CD19-CAR) T cell immunotherapy to treat adults aged 55 years or older who have acute lymphoblastic leukemia (ALL) that is in remission following induction therapy (i.e., “first remission”). In this clinical trial, we will infuse the CD19-CAR T cells early in the treatment sequence, which may prevent the leukemia from returning without additional therapy. This clinical trial aims to give us a better understanding of CD19-CAR T cell safety and activity when given during first remission, with the goal of improving the very poor outcomes of older adults with ALL.

On the basis that T-cell acute lymphoblastic leukemia (T-ALL) cells overexpress IL-7 receptor (IL7R), which promotes chemotherapy resistance and relapse, we developed IL7R-targeted chimeric antigen receptor (CAR) T cells with low- and high-affinity single-chain variable fragments (scFvs). Following extensive investigation, we established the antitumor efficacy of low-affinity IL7R CAR against T-ALL cells in vitro, in vivo and against patients’ T-ALL blasts using their own T cells transduced with IL7R CAR. With data establishing tumor specificity and antitumor efficacy, and a novel manufacturing method of ‘natural selection’ to seamlessly manufacture a large number of IL7R CAR T cells from patients with T-ALL, we are now proceeding with Investigational New Drug studies to initiate a phase I clinical trial in 2025 Q4.

CD7-CAR T cells with CD7-PEBL represents an innovative technology that enables the production of CAR T cells able to escape the fratricide for the treatment of relapsed/refractory T-ALL. At Bambino Gesù Children’s Hospital, in collaboration with Prof. Campana (Singapore), we have tested the safety of these CAR T cells in children/young adults with relapsed/refractory T-ALL obtaining promising results, in terms of both safety and efficacy. We now aim to activate a Phase 2 multicenter study to further explore the efficacy of this approach.

The combination of hypomethylating agents (HMA) and venetoclax (Ven) is a standard of care to treat acute myeloid leukemia (AML). However, HMA+Ven is not curative, and most patients will ultimately relapse without effective treatment options available thereafter. Our institution has discovered a novel AML target and pioneered the development of a best-in-class chimeric antigen receptor T cell therapy (CART64) for patients who have relapsed after HMA+Ven treatment. We now propose to demonstrate safety and effectiveness of CART64 in a phase 1, first-in-human, clinical trial in patients with advanced AML and high-risk myelodysplastic syndromes (HR-MDS).

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.

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.

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).

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.

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.