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REACH: Recruitment Expansion through community Access to Clinical trials in Hematologic malignancies

Mayo Clinic Rochester (MCR) is a tertiary center with 35,000 blood cancer visits annually. Circa 70% of patients referred to MCR come from 5 states: MN, WI, IA, SD and ND inhabited by 10,483,946 people living primarily in a rural setting. To improve local care access, MCR has developed the Mayo Clinic Health System (MCHS), a network of 17 community sites of which 7 have oncology care. In 2018, the MCR joined with the University of Minnesota to establish the Minnesota Cancer Clinical Trials Network (MCCTN) that includes 18 sites.

Pan-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.

A phase 1 study of DR-0201, a bispecific myeloid engager, in patients with B-NHL

In November 2022, LLS made an equity investment in Dren Bio to "Support Clinical Development of the DR-01 Program for Rare Leukemia & Lymphoma Indications Including Large Granular Lymphocyte Leukemia (LGLL) and Cytotoxic Lymphomas."

Language Matters: What Supporters Say is Not Always What People with Cancer Hear

A Starting Place to Prioritize Your Mental Health

Coping with a blood cancer diagnosis and the whirlwind of experiences that follows can be physically, mentally, and emotionally draining for everyone impacted by it. 

Whether you're a patient or caregiver, you begin to realize your life will never be the same. 

A phase 2 study of BI-1808, a monoclonal antibody to TNFR2, as a single agent and in combination with pembrolizumab in patients with solid tumors and CTCL

In January 2023, LLS made an equity investment in BioInvent to "Support Clinical Development of BI-1206 for NHL Indications and BI-1808 for T-Cell Lymphoma Indications Including CTCL."

A phase 1 study of CB-010, a CRISPR-edited allogeneic CAR-T targeting CD19, in patients with B-cell NHL

In February 2021, LLS made an equity investment in Caribou Biosciences to support "A Phase 1, Multicenter, Open-Label Study of CB-010, a CRISPR-Edited Allogeneic Anti-CD19 CAR-T Cell Therapy in Patients With Relapsed/Refractory B Cell Non-Hodgkin Lymphoma." Caribou is a leading clinical-stage biotechnology company, co-founded by CRISPR pioneer and Nobel Prize winner Jennifer Doudna, Ph.D., using next-generation CRISPR genome-editing technology to develop “off-the-shelf” (allogeneic) CAR therapies for hard-to-treat blood cancers.

Targeting Siglec15 to promote immune response to malignant B cells

The goal of this project is to explore a novel immunologic therapeutic target for hematologic malignancies, SIGLEC15 (Sig15). The central hypothesis is that Sig15 is aberrantly expressed in malignant B cells, is released to attenuate immune responses and can be targeted therapeutically to promote immune responses to malignant hematopoietic cells. This work will accelerate therapeutic exploitation of the immune system for the treatment of leukemia and lymphoma by targeting Sig15.

Prediction and prevention of therapy-related myeloid neoplasms following autologous transplantation

The proposed studies will identify alterations in hematopoietic regulation that predict for risk for therapy-related myeloid neoplasm (TMN) and improve understanding of disease evolution to guide strategies to prevent TMN in patients receiving autologous hematopoietic cell transplantation (aHCT) for lymphoma. They will investigate alterations in hematopoietic function in peripheral blood stem cell used for aHCT, and serial evolution of hematopoietic defects leading to development of TMN.

Peer-to-Peer Support

Patti Robinson Kaufmann First Connection® Program

If you or a family member has been diagnosed with a blood cancer, you may find it helpful to speak with someone who has gone through a similar experience and learned how to manage the same disease you're trying to cope with each day. The Patti Robinson Kaufmann First Connection® Program is a free service of The Leukemia & Lymphoma Society (LLS) that introduces patients and their loved ones to a trained peer volunteer who has gone through a similar experience.

Cell-free DNA analysis of persistent CAR T-cell populations in humans

The focus of this research project is to understand how therapeutic chimeric antigen receptor (CAR) T-cells mediate long-term remission of diffuse large B-cell lymphomas. I will use cell free DNA collected from patient plasma to understand if there is an association of CAR T-cell persistence and long-term tumor remission. The goal of this research is to define how CAR T-cells suppress tumors over time to develop better CAR T-cells in the future.

TCR directed immunotoxins and antibody drug conjugates for the treatment of T cell malignancies

Few treatment options are available for T cell leukemias and lymphomas, collectively called T cell cancers that affect ~100,000 patients worldwide each year. The current proposal will generate new antibodies attached to drugs and toxins that kill the T cell cancers. Importantly, the antibodies will preserve enough healthy T cells to maintain a functioning immune system. These modified antibodies may improve patient outcome and limit side effects associated with traditional chemotherapies.

Targeting 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.

Stratified treatment of newly diagnosed MCL based on the presence or absence of high risk features utilizing non-cytotoxic agents.

We believe that regimens without chemotherapy can induce significant and durable remissions in patients with Mantle cell lymphoma (MCL). We will confirm this hypothesis by conducting two clinical trials stratified by the presence or absence of high risk features. We will utilize BH3 profiling and MRD testing to assist with predicting treatment response and remission. Our goal is to verify the efficacy of our regimen and prove the utility of BH3 profiling and MRD testing in outcome prediction.

Improving Bispecific CD20/CD19 CAR T-cell Therapy to Overcome Resistance Mechanisms in B-cell Malignancies

The objective of this proposal is to improve bispecific anti-CD20/anti-CD19 CAR T-cell activity and persistence by understanding impact of cell manufacturing parameters on final engineered CAR-T product and determining resistance mechanisms in relapsing patients. We will analyze patient apheresis, final CAR-T product, and peripheral blood samples from subjects enrolled on an ongoing clinical trial (NCT04186520). Data from these studies will advance CAR T-cell therapies for lymphoma patients.

Interrogating T-cell apoptotic priming to improve CAR-T persistence in treatment of lymphoid malignancies

CAR-T cells are made from a patient’s own immune cells, altered so that they specifically recognize and kill the patient’s cancer cells. They are effective in many but not all cases of B-acute lymphoblastic leukemia (B-ALL) and diffuse large B-cell lymphoma (DLBCL), among other blood cancers. In this proposal we seek to better understand ways to select T cells that will make better CAR-T cells as well as to treat CAR T cells them in ways to make them work better in the cancer patient.

Understanding Resistance Mechanism to Enhance CAR-T Immunotherapy for MCL

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.

Analysis and Targeting of Tumor-Associated Monocytes/Macrophages that Inhibit PD-1 Blockade

Inhibition of a tumor-triggered immune exhaustion pathway, termed PD-1 blockade, enables immune effector cells to attack cancers. In classic Hodgkin Lymphoma (cHL), PD-1 blockade is now a standard treatment for relapsed disease and a component of experimental frontline therapy. We have identified a major population of monocyte/macrophages in patients with cHL that inhibit tumor cell killing and limit the efficacy of PD-1 blockade.

Family Support Groups

The Leukemia & Lymphoma Society (LLS) Family Support Groups program gives patients and their families a place to go where they can share information, education and feelings in a comfortable and caring environment. Family Support Groups are for anyone affected by blood cancer and are free. There are currently 230 groups near some of our chapters and in outlying areas, with the number of groups growing each year. Groups generally meet once a month at a library, a local conference room or at LLS's chapters.

Defining ctDNA monitoring and immune modulation in a novel, risk stratified clinical trial for PTLD

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.

Therapy Acceleration Program - Portfolio

Since 2017, three TAP-supported therapies have been approved by the U.S.

Developing Novel CAR-T Cell Therapy For Hematologic Malignancies

We observed that patients with many hematologic cancers expressed high levels of DKK1 and generated novel human DKK1-A2 CAR-T cells that can kill cancer cells from HLA-A2+ patients with myeloma, lymphoma, or leukemia. We also found that Th9-polarized T cells have enhanced antitumor effects in vivo. In this proposal, we will determine 1) whether and how Th9-polarized DKK1-A2 CAR-T cells are promising effector T cells for immunotherapy of human patients, and 2) whether Th9-polarized DKK1-A2 CAR-T cells are associated with reduced on- and off-target toxicities.

The 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.

Novel CD7 CAR T-cells for refractory T-cell malignancies affecting pediatric and AYA patients

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.