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.

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.

To improve the cure rate of patients suffering from acute myeloid leukemia (AML), our study aims to target resistant leukemia stem cells by developing an 'antibody-drug conjugate' (ADC) against CD99, a protein expressed on these cells. Initial tests of two ADC versions have shown promise in combating AML. Our next steps involve refining the anti-CD99 antibody, identifying the optimal drug for conjugation, and testing the ADC on patient-derived leukemia models. Completing these objectives will pave the way for a phase 1 clinical trial, offering a potentially transformative treatment for AML.

In October 2023, LLS made an equity investment in Vittoria to "Support Clinical Development of VIPER-101, a CAR-T Cell Therapy for T-cell lymphomas."

Vittoria Biotherapeutics is developing novel CAR-T cell therapies that transcend the limitations of current cell therapies. Based on technology exclusively licensed from the University of Pennsylvania, Vittoria's proprietary Senza5 platform unlocks the antitumor potential of engineered T cells and utilizes a five-day manufacturing process to maximize stemness, durability, and target cell cytotoxicity. By acting on the fundamental biology of T cells, Senza5 can be used to improve the efficacy of engineered T cell therapies with pipeline applications in oncology and autoimmune diseases.

Vittoria aims to conduct a Phase 1 dose escalation clinical trial for its lead program VIPER-101, an autologous, dual population CD5-knockout CAR-T cell therapy for T-cell Lymphoma featuring the novel Senza5 platform technology. The Phase 1 trial is ongoing to assess the safety and efficacy of VIPER-101 in patients with T-cell lymphomas (NCT06420089).

CMML is a universally lethal blood cancer characterized by increased monocytes (a type of white blood cell) in the peripheral blood and abnormal appearing cells within the bone marrow. Most CMML patients are clinically asymptomatic and remain so for weeks to months following diagnosis, with disease progression remaining inevitable. Despite therapeutic advances in similar blood cancers, no specific molecularly targeted therapies currently exist to treat CMML. Our team aims to identify new therapies and repurpose existing therapies to address the emergent unmet need for new treatments that meaningfully improve, and extend, the lives of patients with CMML.

hypothesize that demonstrating activity of CLL-1 CAR-T (CLL1CART) cell therapy with or without trametinib in pre-clinical models of chronic myelomonocytic leukemia (CMML) and juvenile myelomonocytic leukemia (JMML) is the most efficient method to bring cellular therapy to patients with these orphan diseases. In Aim 1, we will determine the in vitro and vivo efficacy of CAR-T cells redirected against CLL-1 using patient-derived xenograft (PDX) models of CMML and JMML. In Aim 2, we will evaluate the role of combining trametinib with CLL1CART cells. Based on our preliminary data, we hypothesize that trametinib will have direct antileukemia activity and will increase the efficacy of CLL1CART by decreasing T-cell exhaustion and augmenting T-cell fitness.

We are aiming to bring a new treatment option to patients with chronic myelomonocytic leukemia (CMML) by utilising CCL2-drug conjugates that specifically target and eliminate cancerous cells. Our leading conjugate shows potent and selective efficacy in killing CMML cells. The proposed work will help us understand how this drug works, which patients are most likely to benefit and how it can be combined with current treatments to achieve the greatest patient benefit.

We will test the efficacy of CAR T cell therapy for CMML. We will modify the tumor microenvironment to enhance their efficacy. and we will upscale CAR T cells to the next level in terms of their genetic structure.

In October 2023, LLS made an equity investment in Enterome to "support the ongoing Phase 2 SIDNEY study of EO2463 in indolent non-Hodgkin B-cell lymphoma."

Enterome is a clinical-stage biopharmaceutical company developing breakthrough immunomodulatory drugs for the treatment of cancer and immune diseases. Enterome’s pioneering approach to drug discovery is based on its unique and powerful bacterial Mimicry drug discovery platform, allowing it to analyze and uncover new biological insights from the millions of gut bacterial proteins in constant cross-talk with the human body. Its first-in-class small protein and peptide drug candidates modulate the immune system by closely mimicking the structure, effect or actions of specific antigens, hormones, or cytokines. 

EO2463 is a clinical-stage off-the-shelf OncoMimics™ peptide-based immunotherapy. It combines four microbial-derived OncoMimics™ peptides that closely mimic specific cytotoxic T cell (CD8+ T cell) epitopes in B cell Tumor-Associated Antigens CD20, CD22, CD37, and CD268 (BAFF receptor), as well as a helper CD4 peptide, UCP2. The SIDNEY trial is a multicenter, Phase 2 trial investigating EO2463 in monotherapy and in combination with standard of care - rituximab and rituximab in combination with lenalidomide – for treatment of patients with indolent NHL (NCT04669171).

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).