Search Results
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.A phase 1/2 study of BI-1206, a monoclonal antibody to CD32b (FcyRIIB), in combination with rituximab in patients with indolent NHL that has relapsed or is refractory to rituximab
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."Targeting HSP70 to Immune Effector Cells to Overcome the Immune Suppressive Myeloma Microenvironment
Development of a strong anti-cancer immune response requires coordinated action of the innate and adaptive parts of the immune system, but cancer cells alter their environment to suppress virtually every step in this process, which promotes cancer progression and treatment resistance. One promising strategy could be to target Heat shock protein 70 (HSP70), which plays an important role in both innate and adaptive immunity, and we therefore developed a series of novel antibodies to HSP70, one of which cured mice of multiple myeloma.A phase 2 trial of EO2463, a novel microbial-derived peptide therapeutic vaccine, as monotherapy, and in combination with lenalidomide and rituximab, for treatment of patients with indolent NHL
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."Epigenetic Mechanisms and Targeting in Hematological Malignancy
Blood cancers can be caused by aberrant regulation of genes that control cell growth and development. The root cause of this problem may be the presence of mutant regulator proteins in the cell and abnormal switching on or off of target genes. Our SCOR studies the molecular basis of this gene deregulation using cell cultured in the laboratory, in human specimen and animal models.Asistencia Financiera Local
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NHL Subtypes
More than 60 specific NHL subtypes have been identified and assigned names by the World Health Organization (WHO). NHL subtypes are categorized by the characteristics of the lymphoma cells, including their appearance, the presence of proteins on the surface of the cells and their genetic features. It's important to know your subtype since it plays a large part in determining the type of treatment you'll receive. A hematopathologist, a doctor who specializes in the diagnosis of blood disorders and blood cancers, should review your biopsy specimens.
Christina
As a Greek Latina indie author, I found it empowering to share my fight with lymphoma through social media and with my current writing. Many have told me that it’s inspiring, and I hope that leads to more attention and support for those fighting blood cancers like lymphoma.
Hollis
I was diagnosed with lymphoma in January and it has been an uncertain journey since then. I’m still unsure of what lymphoma means to me. Because I haven’t been able to answer this question, I have been reticent to share my diagnosis with others. Am I a cancer “victim?” Does cancer define me? Should I be advocating for Lymphoma care and awareness this September? I’m far from the first person to grapple with a cancer diagnosis, but this month I am compelled to finally share my Lymphoma diagnosis.
Treatment for Aggressive NHL Subtypes
Aggressive non-Hodgkin lymphoma (NHL) progresses rapidly. It makes up about 60 percent of all NHL cases in the United States. Aggressive subtypes include:
Erica
Erica was diagnosed with potentially fatal Stage 4 Hodgkin Lymphoma on March 28, 2013. Her journey to survive her battle with cancer was very trying but after overcoming her obstacles, Erica is very passionate about inspiring people to have the d’zire to survive any challenges that they may face in their lives. Erica’s fight to survive lymphoma had its highs and its lows, however, she didn’t give up even when at times her battle seemed like it wasn’t getting any easier.
Kenneth
On August 24, 2017, I was diagnosed with Hodgkin lymphoma (HL). It turns out, after much back-and-forth and a second cervical excision, that I actually had diffuse large B-cell lymphoma (DLBCL), a type of non-Hodgkin lymphoma (NHL). And for good measure, kidney cancer as well. Why not two primaries, right?
Max
My son Max was diagnosed with B-cell lymphoma in May 2017, just 10 days before his 19th birthday. He discovered a lump under his chin a few months before, and in April he noticed it had grown. After we took him to get it checked out and learned the devastating news, we were in complete shock. He had no other signs of anything else being wrong.