Research We Fund
With hundreds of projects currently underway, we fund scientists through our academic grant programs and biotech partners through our strategic venture philanthropy initiative. Use the filters below to find an LLS-funded project.
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George Vassiliou, MBBS, PhD
University of Cambridge
CambridgeDevelopment of a clinical program for myeloid cancer prevention
The majority of myeloid cancers remain incurable. We previously showed that individuals at risk can be identified years in advance, indicating that prevention may be a viable alternative to treatment. Here, we propose a program of work to establish a clinical platform for myeloid cancer prevention. This includes development of a screening strategy, improved understanding of myeloid cancer evolution, identification of treatment targets and establishment of a specialized clinic to deliver therapy.
Program: Specialized Center of Research ProgramProject Term: Start Date: February 1, 2024 End Date: January 31, 2029
Todd Fehniger, MD PhD
Washington University in St. Louis
St. Louis, WashingtonDeveloping Novel Immunotherapies for Challenging Lymphomas
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.
Program: Specialized Center of Research ProgramProject Term: Start Date: October 1, 2023 End Date: September 30, 2028
Craig Jordan, PhD
University of Colorado Denver, Anschutz Medical Campus
Aurora, ColoradoTherapeutic targeting of AML stem cells 2023
The goal of this SCOR project is to identify and eradicate the root cause of acute myeloid leukemia, the so-called leukemia stem cell (LSC). In the previous cycle of this SCOR grant, we developed two unique strategies, each of which efficiently eradicates LSCs in the laboratory. Going forward, we will expand our scientific efforts to further improve these approaches and also conduct clinical trials to determine whether our approaches to killing LSCs will benefit AML patients.
Program: Specialized Center of Research ProgramProject Term: Start Date: October 1, 2023 End Date: September 30, 2028
Tak Mak, PhD
Princess Margaret Cancer Centre, University Health Network
Toronto, OntarioThe Immune Niche in the Development of Hematological Malignancies and Implications for Novel Therapy
Our SCOR Program, composed of four complementary Projects supported by three shared Cores, is designed to determine how the immune niche and factors in its composition and regulation affect the initiation and progression of hematopoietic malignancies. Using genetically engineered mouse models, cell cultures and patient samples, the power of multi-omics analyses will be brought to bear to identify common drivers and expose underlying mechanisms. Findings from this work should reveal multiple candidate therapeutic targets whose exploitation may lead to the development of broadly applicable therapeutics for leukemias/lymphomas. Partnerships with pre-clinical and clinical trials experts at our home institutions and beyond will facilitate the translation of our findings to the bedside and potentially provide new hope to patients suffering from these devastating cancers.
Program: Specialized Center of Research ProgramProject Term: Start Date: October 1, 2022 End Date: September 30, 2027
Robert Soiffer, MD
Dana-Farber Cancer Institute
Boston, MassachusettsUnderstanding and Overcoming Mechanisms of Immune Evasion after Allogeneic Transplant
Outcomes for patients with acute myelogenous leukemia who relapse after transplantation are dismal. This SCOR brings together an international group of collaborators with deep expertise in genomics, epigenetics, antigen presentation, and immune-regulation. They will focus on mechanisms of immune evasion by leukemia cells, identifying effective T cell responses to those evasive processes, and providing critical insights into the optimal approaches to model new and promising targets for immunotherapy with a goal of eliminating leukemia recurrence.
Program: Specialized Center of Research Program
Project Term: Start Date: October 1, 2022 End Date: September 30, 2027
Timothy Graubert, MD
Massachusetts General Hospital
Boston, MassachusettsExploiting Vulnerabilities in RNA Splicing to Treat Hematologic Malignancies
RNA splicing is a central metabolic pathway that is frequently perturbed in hematopoietic malignancies (HMs) that harbor mutations in spliceosome components (most commonly affecting SRSF2, SF3B1, U2AF1, or ZRSR2). These mutations are particularly prevalent in myeloid malignancies (e.g., MDS, MDS/MPN, sAML), but recent pan-cancer studies have implicated aberrant splicing in >30 tumor types. The Project Leaders have probed the molecular consequences of aberrant splicing and identified critical pathways that are amenable to targeted inhibition, including the DNA damage response (Graubert/Walter), the nonsense-mediated RNA decay (NMD) pathway (You/Walter), the spliceosome itself (Abdel-Wahab/Walter/Graubert), and others. To date, effective therapies for HMs have not capitalized on these unique vulnerabilities. The goal of this SCOR is to generate testable clinical hypotheses based on careful mechanistic studies in pre-clinical models and to rapidly move these ideas into the clinic in the near term.
Program: Specialized Center of Research ProgramProject Term: Start Date: October 1, 2021 End Date: September 30, 2026
Steven Horwitz, MD
Memorial Sloan Kettering Cancer Center
New York, New YorkTranslational Discovery in Peripheral T-Cell Lymphomas
Peripheral T-cell lymphomas (PTCLs) are poorly understood and patients with PTCL are underserved by current therapies. The most common subtypes (among >20) are PTCL-not otherwise specific (NOS), angioimmunoblastic T-cell lymphoma (AITL), and anaplastic large cell lymphoma (ALK- ALCL). Rational treatment strategies for these lymphomas are lacking, largely due to the insufficient characterization of PTCL pathobiology and historic paucity of faithful models. Over the past 4 years, our groups and others have identified recurrent alterations in PTCL subsets, developed targeted agents against PTCL and established an unprecedented repository of PTCL models for in vitro and in vivo interrogation. A clinical trial led by director Dr. Horwitz established a new standard-of-care for upfront treatment of CD30+ PTCLs. Additional trials developed through this SCOR have advanced therapeutics targeting PI3 kinase (duvelisib), JAK1/2 (ruxolitinib) and IDH2 (enasidenib) for relapsed/refractory PTCL. The central goal for the next 5 years of support is to establish informed combination strategies that eradicate resistant populations and thereby extend the duration of meaningful responses.
Program: Specialized Center of Research ProgramProject Term: Start Date: October 1, 2021 End Date: September 30, 2026
Soheil Meshinchi, PhD, MD
Fred Hutchinson Cancer Research Center
Seattle, WashingtonMulti-modal Immunotherapeutic Targeting of AML-restricted Targets in Infants and Children
Advances in understanding and management of AML in children has been stagnant for decades. Observed improvements in survival are more directly linked to improvements in supportive care or risk identification rather than advances in therapeutics. Excitement around FDA approval of two new IDH1/2 inhibitors did not reach the pediatric oncology community given paucity or absence of such mutations in children. This also highlights the stark differences between AML in older adults and that in younger patients. Thus, “trickle down therapeutics” where therapies that are developed in older adults are used effectively in children is a flawed concept. Discoveries and therapeutic development in younger patients must be prioritized if meaningful advances are to be made in curing AML in younger patients. Given that AML in children is not a priority for the pharmaceutical companies, alternate mechanisms for advancing therapeutics in children and young adults should be implemented.
Program: Specialized Center of Research ProgramProject Term: Start Date: October 1, 2021 End Date: September 30, 2026
Stephen Nimer, MD
University of Miami
Coral Gables, FloridaInterventional Epigenetics in Myeloid Malignancies
Myeloid malignancies like acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and myeloproliferative neoplasm (MPN) arise due to a combination of genetic mutations and epigenetic abnormalities that sustain the abnormal behavior of cancer cells. The genetic material of the cell is the “hard drive” full of instructions that allow cells to grow, have unique functions, and ultimately live or die. Epigenetics is the “software” of the cell, allowing access to the information from the hard drive in a controlled manner. This interplay between the hardware and the software culminates in gene expression, allowing the genetic material to be read and interpreted. Targeted therapy in other myeloid cancers only works for a fraction of patients. Most myeloid cancers have a constellation of mutations that, in combination, likely determine the outcome of patients. The genetic mutations in myeloid cancers often occur in genes that control the epigenetic regulation of gene expression. While it is not possible to correct the genetic abnormalities in cancer cells, it is becoming possible to target and reverse the epigenetic abnormalities, and either kill the cancer cell or make it behave more normally. The goal of this SCOR is to analyze basic mechanisms of disease in order to arrive at novel therapeutic strategies and develop biomarkers that can predict the likelihood of a therapeutic response.
Program: Specialized Center of Research ProgramProject Term: Start Date: October 1, 2017 End Date: September 30, 2022
Robert Orlowski, PhD, MD
The University of Texas MD Anderson Cancer Center
Houston, TexasSCOR in High Risk Plasma Cell Dyscrasias
Dr. Orlowski assembled an experienced, collaborative group of researchers who work in a multidisciplinary manner on projects focusing on basic, translational, and clinical aspects of smoldering multiple myeloma (SMM) and multiple myeloma (MM). Both high risk SMM and MM represent important and urgent unmet medical needs for the development of novel, more effective therapies.
Program: Specialized Center of Research ProgramProject Term: Start Date: October 1, 2017 End Date: September 30, 2022
Carl June, MD
The Trustees of the University of Pennsylvania, Medical Center
Philadelphia, PennsylvaniaPan-heme CAR: Anti-CD38 CAR T cells for myeloid, lymphoid and plasma cell malignancies
Our SCOR team has a razor-sharp focus on an exciting new treatment modality for blood cancers: chimeric antigen receptor (CAR) T cells. T cells can be trained to target cancer cells by genetic modification. In fact, previous support from the Leukemia & Lymphoma Society allowed us to successfully develop CAR T cells targeted to CD19, a pan-B cell marker. This treatment, generically called CART-19, was approved by the FDA in 2017 for the treatment of B-cell acute lymphoid leukemia (B-ALL) and in 2018 for some non-Hodgkin lymphoma (NHL), with promising results in other B cell malignancies such as chronic lymphocytic leukemia (CLL). Thus, the development of a single therapy for a single disease (initially, CLL) paid handsome dividends when translated to a broader range of CD19-expressing malignancies (ALL, NHL).
Program: Specialized Center of Research ProgramProject Term: Start Date: October 1, 2019 End Date: September 30, 2024
Craig Jordan, PhD
University of Colorado Denver, Anschutz Medical Campus
Aurora, ColoradoTherapeutic targeting of AML stem cells 2018
Our SCOR team seeks to fundamentally reinvent the ways in which physicians diagnose and treat acute myeloid leukemia (AML). For over 40 years, AML has been treated with a combination of chemotherapy drugs that have major side effects and usually only provide short-term benefit to patients. Indeed, survival rates for most AML patients are dismal, and quality of life for these patients is poor. Consequently, improved strategies for AML are a huge priority for the field. We believe that the lack of progress against AML is due to a single, fundamental failure of existing therapies: While current therapies attack leukemia cells, they fail to act against the real root of the problem, namely leukemia stem cells. It’s like mowing over weeds in a lawn. If the roots are not removed, the weed (disease) will grow back. And like eradicating the roots of weeds, AML stem cells have proved difficult to treat. This is primarily due to the fact that AML stem cells within a given patient can exist in multiple forms, each of which has a differing response to therapy. In other words, while various drugs can often kill some AML stem cells in a patient, completely eradicating all the AML stem cells can be very difficult.
Program: Specialized Center of Research ProgramProject Term: Start Date: October 1, 2018 End Date: September 30, 2023
Helen Heslop, MD
Baylor College of Medicine
Houston, TexasImmunotherapy of Hematologic Malignancies
The overall goal of this SCOR proposal is to develop and clinically validate T-cell immunotherapies designed to produce antitumor activity without the toxicities associated with intensive chemotherapy. The effectiveness of T-cell immunotherapy for leukemia and lymphoma has now been amply demonstrated. Studies conducted in our previous SCOR have already led to multicenter trials and orphan drug designation of EBV-specific T cells for the treatment of EBV-positive NHL and to commercial licensing of our genetically modified T cells and a genetic safety switch engineered into effector T cells.
Program: Specialized Center of Research ProgramProject Term: Start Date: October 1, 2018 End Date: September 30, 2023
Jonathan Licht, MD
University of Florida
Gainesville, FloridaTargeting Enhancer Dysfunction in Hematological Malignancy
Blood cancers such as leukemia, lymphoma and myeloma may be caused by abnormal regulation of genes that control normal cell growth and development. Genes that are normally active can be silenced and/or genes normally not present in a blood cell are abnormally activated. The result can be an uncontrolled signal for continued cell growth or survival. Our group studies the molecular basis of this gene deregulation using cells cultured in the laboratory, human specimens, and animal models.
Program: Specialized Center of Research ProgramProject Term: Start Date: January 1, 2019 End Date: September 30, 2024
Madhav Dhodapkar, MBBS
Emory University
Atlanta, GeorgiaImproving targeted adoptive cell therapy of myeloma
Dr. Madhav Dhodapkar, M.D., of Winship Cancer Institute of Emory University, Atlanta, leads a multi-institutional, multi-disciplinary LLS Specialized Center of Research team focused on advancing new immunotherapies for patients with multiple myeloma. Their goal is to improve the effectiveness of CAR T-cell immunotherapy, which engineers the patient’s T cells to find and kill cancer cells. The CAR-T they are studying targets a protein called BCMA found on the surface of all myeloma cells. BCMA-targeting therapies are showing tremendous promise for treating myeloma patients in clinical trials, but many patients eventually relapse. Dr. Dhodapkar’s group is working to understand the mechanisms that cause some patients to be resistant to the treatment. They are also investigating another type of immunotherapy that relies on natural killer T cells. His team includes researchers at Emory as well as Fred Hutchinson Cancer Center in Seattle.
Program: Specialized Center of Research ProgramProject Term: Start Date: January 1, 2020 End Date: December 31, 2024