Research we fund

Albert Einstein College of Medicine

Myelodysplastic neoplasms are malignant disorders driven by expansion of diseased hematopoietic stem cells and progression to leukemia. Our investigations have identified the important role of the transporter of amino acid glutamine SLC38A1 in sustaining metabolic demands of rapidly growing malignant stem cells. The goal of this project is to genetically target this transporter to understand its role on tumorigenesis and progression; and to develop SLC38A1 inhibitors as novel therapeutic tools.

Program Name(s)

Discovery

Monash University

As a lymphoma develops it expresses genes that are normally silenced to convey a survival advantage. When these genes are on the X or Y (sex chromosomes) they may present a gender-specific therapeutic target. We have identified a gene (DDX3X in females or DDX3Y in males) that is reactivated in lymphomas such that the lymphomas cannot survive if this gene is removed. This project will develop new ways to inhibit DDX3X and Y as a novel treatment for poor-risk and aggressive lymphoma.

Program Name(s)

Translational Research Program

Universite de Lausanne

In the Cancer Immunology field, the “aging” variable has not been investigated profoundly yet, even though aging is the first factor associated to cancer. This represents a major limitation on the significance of the experimental results and their translation to the clinic. We believe that with our proposal we can shade light on important biological processes which drive immunotherapy failure. We have shown that T cell function is dependent not only on the differentiation state but also on their biological age. Thus, taking in consideration aging and the age-driven metabolic defects in T cells will help to better understand their biology and develop better strategies to boost immunotherapy.

Program Name(s)

Translational Research Program

University of Arkansas for Medical Sciences

We have observed that non-glycosylated CST6 proteins suppress osteoclast differentiation and function without causing immunosuppression. We aim to determine whether BCMA-CAR-T cells which are engineered to secret CST6 proteins kill myeloma cells and suppress bone lytic lesions without immune suppressive effects in myeloma. Our ultimate goal is to develop a CAR-T-cell based immune therapy to prevent bone loss and disease progression in myeloma patients.

Program Name(s)

Translational Research Program

MD Anderson Cancer Center

TP53-Y220C is a recurrent hotspot TP53 mutation observed predominantly in AML and MDS among hematological malignancies. This study aims to investigate the mechanism of action and therapeutic activity of PC14586, a compound designed to bind p53-Y220C protein and stabilize it in the wild-type conformation and to develop mechanism-based combinations that improve its efficacy in TP53-Y220C mutant AML.

Program Name(s)

Translational Research Program

Follicular lymphoma is a common form of blood cancer, affecting 15,000 new patients annually in the United States, but it remains incurable with conventional treatments. Bispecific antibodies represent a new class of therapies that engage the immune system to attack lymphoma cells and have shown promising effectiveness in inducing remissions in patients with this disease, but even they are unlikely to be curative. Researchers from the Dana-Farber Cancer Institute here propose to analyze lymphoma cells from patients undergoing treatment with bispecific antibodies on several complementary clinical trials to determine how these cells evade the immune system and develop resistance. It is believed that such mechanisms of resistance may reveal vulnerabilities within the lymphoma cells that novel treatments can overcome in combination with bispecific antibodies to cure patients with follicular lymphoma.

Program Name(s)

Translational Research Program

Emory University

Despite remarkable progress in the last 20 years, multiple myeloma remains an incurable disease. In recent years, 2 CAR T cell products that target BCMA on the myeloma cell have been approved. These products result in remarkable initial responses however the duration of these responses has been disappointing. In this proposal, we will take a novel approach to isolate and characterize myeloma cells that interact with CAR T cells but are not killed by them as a potential resistance mechanism.

Program Name(s)

Discovery

University of Virginia

Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma characterized by resistance to standard treatments and short survival. For the 2023 LLS MCLII Synergistic Team Award, we have assembled a team of leaders in basic, translational, and clinical research in MCL to tackle the current significant obstacles in understanding and treating MCL. In the last decade, we investigated the therapy resistance mechanism of MCL, and pioneered clinical trials for targeted therapies (ibrutinib, lenalidomide) and chimeric antigen receptor T-cell (CAR-T) therapy. However, despite these dramatic advancements, resistance to these newer therapies, including targeted therapy and CAR-T cells, is seen in over 50% of patients. Thus, it remains an unmet need to better define the mechanisms of resistance and then develop rationally designed strategies to overcome resistance. The overall goal of this Synergistic Team Award is to develop improved curative therapies for patients with MCL at relapse. The goals will be addressed in three highly focused, independent but highly integrated projects that utilize state-of-the-art genomic technologies, patient-derived xenograft models, clinical data and primary MCL samples. With the joint effort of our laboratories, highly interactive and accomplished scientists, and physician researchers from multiple institutions with expertise in MCL and therapy, we are uniquely poised to develop improved next-generation of combination therapy for relapsed MCL patients.

Program Name(s)

Mantle Cell Lymphoma Research Initiative

TAP Partner

In August 2013, LLS began its first European partnership with Affimed that supported two clinical trials for Hodgkin lymphoma (HL) patients. Expanding upon the initial work supported by LLS TAP, Affimed is currently enrolling "A Phase 2 Study of Innate Cell Engager AFM13 in Combination With Allogeneic Natural Killer Cells (AB-101) in Subjects With Recurrent or Refractory Hodgkin Lymphoma and CD30 Positive Peripheral T-Cell Lymphoma."Affimed is a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer by actualizing the untapped potential of the innate immune system using the proprietary ROCK® platform to enable a tumor-targeted approach to recognize and kill a range of hematologic and solid tumors.AFM13 is bispecific tetravalent engager targeting CD30 on tumor cells and CD16A on NK cells and macrophages. AFM13 in combination with AB-101 (allogeneic natural killer cells) is currently in a Phase 2 clinical trial in relapsed or refractory Hodgkin lymphoma or CD30-positive PTCL (NCT05883449).

Program Name(s)

Therapy Acceleration Program

New York University School of Medicine

Coming soon.

Program Name(s)

Special Grants

The Brigham and Women’s Hospital

The focus of my research is to evaluate the efficacy of and to unravel the molecular mechanisms underpinning a novel drug combination in AML targeting oncogenic protein translation and apoptosis. We will utilize genetic perturbation and other orthogonal approaches, including in vitro and ex vivo assays, and in vivo AML PDX models. The goal of my research is to transform the clinical management of AML patients, particularly for relapsed and difficult-to-treat subgroups.

Program Name(s)

Career Development Program

TAP Partner

In July 2012, LLS began its partnership with Constellation to support three first-in-human Phase 1 clinical trials for blood cancer patients and the partnership led to the ongoing trial "A Phase 3, Randomized, Double-blind, Active-Control Study of CPI-0610 and Ruxolitinib vs. Placebo and Ruxolitinib in JAKi Treatment Naive MF Patients."Constellation Pharmaceuticals was a clinical-stage biopharmaceutical company developing novel therapeutics that selectively modulate gene expression to address serious unmet medical needs in patients with cancer. MorphoSys acquired Constellation in July 2021 and continues to enroll patients with myeloproliferative neoplasms in multiple clinical studies.Pelabresib (CPI-0610) is a small molecule inhibitor of bromodomain and extra-terminal (BET) proteins. A Phase 3 clinical trial (NCT04603495) of pelabresib in combination with ruxolitinib for myelofibrosis patients that have not been previously treated with Janus kinase inhibitors completed enrollment.

Program Name(s)

Therapy Acceleration Program