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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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Kimberly Stegmaier
Kimberly Stegmaier
MD
Dana-Farber Cancer Institute
United States
Boston, Massachusetts

Advancing New Therapeutic Strategies for Pediatric Acute Leukemias

Dr. Kimberly Stegmaier is performing pre-clinical research to identify promising therapeutic strategies for pediatric leukemia. Pediatric blood cancers comprise about 40% of all pediatric cancers. The most common pediatric blood cancer is acute lymphoblastic leukemia (ALL), which is curable in most patients through the use of chemotherapy. Though beneficial in the short term, destroying the cancer through chemotherapy often leads to long term health problems. For those that do not respond to chemotherapy, there are fewer therapeutic options. Another pediatric blood cancer is acute myeloid leukemia (AML), which is a more aggressive and lethal disease. Therefore, many pediatric acute leukemia patients require better therapeutic options, and a precision medicine approach targeting specific mutations will likely lead to a better clinical benefit.

Program: PedAL
Award Date: Start Date: October 1, 2020 End Date: September 30, 2022
Ravi Majeti
Ravindra Majeti
PhD, MD
Stanford University
United States
Palo Alto, California

Personalized Metabolic Targeting of Epigenetic AML Mutations Through the Alpha-Ketoglutarate Pathway

AML is characterized by founder mutations in epigenetic regulators that perturb alpha-ketoglutarate flux to block differentiation and rewire metabolism exposing new druggable vulnerabilities. By integrating bioenergetics and 5hmC profiling in primary cells, we have discovered unexpected 2-hydroxyglutarate-independent vulnerabilities for TET2, IDH1, IDH2, WT1, and CEBPA mutations. Here, we propose mutation-directed drug development for AML through targeting of the alpha-ketoglutarate pathway.

Program: Translational Research Program
Award Date: Start Date: October 1, 2020 End Date: September 30, 2023
Marcel Spaargaren
Marcel Spaargaren
PhD
Academic Medical Center Amsterdam
Netherlands
Amsterdam

Towards a rational targeted therapy for Waldenstrom's Macroglobulinemia by kinome-centered loss-of-adhesion and synthetic lethality screens

We have previously demonstrated that disrupted retention of the malignant B cells within lymphoid organs is a key mechanism of action of the Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib, underlying its unprecedented high clinical efficacy in the treatment of chronic lymphocytic leukemia, mantle cell lymphoma and Waldenström’s Macroglobulinemia (WM). Unfortunately, apart from innate (primary) resistance, a significant subset of patients who receive prolonged treatment with ibrutinib develop (secondary) therapy resistance. Considering microenvironment-dependence as the Achilles’ heel of WM cells, we hypothesize that induction of homelessness by targeting localization (homing and retention) as well as survival/proliferation of WM cells in their lymphoid organ microenvironment by combination therapy may overcome innate (primary) resistance and prevent acquired (secondary) drug-resistance, providing a powerful strategy to cure WM. Therefore, our aims are: 1) to identify the signaling pathways and kinases (given their druggability) that control WM cell retention and outgrowth; 2) to identify kinases whose inhibition sensitizes WM cells to the anti-adhesive and growth-inhibitory effects of ibrutinib, and 3) to explore and exploit their potential as therapeutic targets for development of novel targeted (combination) therapy for WM patients.

Program: Special Grants
Award Date: Start Date: March 1, 2020 End Date: March 1, 2022
Helen Heslop
Helen Heslop
MD
Baylor College of Medicine
United States
Houston, Texas

Immunotherapy 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. Given our successful track record, we now propose to develop approaches that will enable T-cell immunotherapies to overcome remaining obstacles to broader application. Our application comes from experienced investigators with strong records of interactive research, who have already designed “first-in-man” studies to address one or more of the pivotal questions central to the success of the program. In this SCOR, Projects 1 and 2 continue their focus on EBV+ lymphoma and myeloma, respectively, but take the work in new directions, while Project 3 exploits recent technical advances to target a new malignancy, acute myeloid leukemia (AML). 

Program: Specialized Center of Research Program
Award Date: Start Date: October 1, 2018 End Date: September 30, 2023
NexImmune
NexImmune
United States
Gaithersburg, Maryland

Phase 1/2 Clinical Studies to Evaluate the Adoptive Cellular Therapy Products NEXI-001 (in Patients with Relapsed AML or MDS after Matched Allogeneic HCT) and NEXI-002 (in Patients with Relapsed/Refractory Myeloma)

NexImmune is a clinical-stage biotechnology company developing a novel approach to immunotherapy designed to employ the body’s own T cells to generate a specific, potent, and durable immune response. The backbone of NexImmune’s approach is a proprietary Artificial Immune Modulation (AIM™) nanoparticle technology platform. The AIM technology enables NexImmune to construct nanoparticles that function as synthetic dendritic cells capable of directing a specific T cell-mediated immune response. AIM constructed nanoparticles employ natural biology to engage, activate and expand endogenous T cells in ways that combine anti-tumor attributes of antigen-specific precision, potency and long-term persistence with reduced potential for off-target toxicities. NexImmune’s two lead programs, NEXI-001 and NEXI-002, are in Phase 1/2 clinical trials for the treatment of relapsed AML after allogeneic stem cell transplantation and multiple myeloma refractory to 3 or more prior lines of therapy, respectively.

Program: Therapy Acceleration Program
Award Date: Start Date: October 6, 2017 End Date: October 23, 2021
Ravi Majeti
Ravindra Majeti
PhD, MD
Stanford University
United States
Palo Alto, California

Clonal Evolution of Pre-Leukemic Hematopoietic Stem Cells in Human Myeloid Malignancies

It has been demonstrated that most cases of AML are associated with mutations in multiple genes. Dr. Majeti's studies will provide novel insights into the genetic events and other factors such as the microenvironment that affect in the development of myeloid malignancies, particularly AML. This study will have significant implications for the prevention and treatment of myeloid malignancies, particularly AML.

Program: Discovery
Award Date: Start Date: July 1, 2020 End Date: June 30, 2023
Gongwei Wu
Gongwei Wu
PhD
Dana-Farber Cancer Institute
United States
Boston, Massachusetts

Mechanisms and targeting of TP63-rearrangements in lymphoma

Chromosomal rearrangements involving a gene called TP63 have been found in 5-10% of several subtypes of lymphomas and patients with TP63-rearrangements have dismal outcomes, with nearly 0% of patients surviving 5 years after diagnosis. We investigate the oncogenic mechanisms of TP63-rearrangements to find the unique cancer cell vulnerabilities to this rearrangement using different models. Our study will develop an effective therapeutic strategy for patients with TP63-rearranged lymphomas.

Program: Career Development Program
Award Date: Start Date: July 1, 2019 End Date: June 30, 2022