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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.

Researcher wearing a hair net, N95 mask and gloves injects a liquid into a vial.

The Leukemia & Lymphoma Society's New Chief Scientific Officer Excited about What's Next in Blood Cancer Research

Lore Gruenbaum, Ph.D., was promoted to The Leukemia & Lymphoma Society’s (LLS) Chief Scientific Officer (CSO) following the retirement of longtime CSO Lee Greenberger, Ph.D. on December 31. We talked with Dr. Gruenbaum about her new role and what’s on the horizon for blood cancer research in 2025.

“It’s a privilege to lead a group of dedicated LLS scientists to seek out and fund innovative science for every type of blood cancer,” says Dr. Gruenbaum.

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.

A researcher analyzes a specimen in a test tube.

Blood Cancer Research Poised for Another ‘Banner Year’ in 2024

More than 25,000 medical professionals from across the world came together in December to discuss the latest blood cancer developments during the annual meeting of the American Society of Hematology (ASH). This annual event gives us the opportunity to think about what advances are on the horizon as LLS works to strengthen cures, care and quality of life for people with blood cancer and their families.

What is New in CAR T-Cell Therapy?

CAR T-Cell Therapy and Blood Cancers

CAR T Supergirl and her Superhero Supporters

CAR T-Cell Therapy: Side Effects

A Child’s Guide to CAR T-cell Therapy

Suggested Reading - I'll Be in the Car

I'll Be in the Car By Annette Januzzi Wick
Three Arch Press, 2006, 392 pages
ISBN: 0977485609

A poetic account chronicling the real-life experiences of author Annette Wick as her husband is diagnosed with, and ultimately dies from, leukemia. Poignantly, this story portrays the even greater challenge for the caregiver - finding life after losing someone so important to every aspect of who you are. For anyone who has or will experience loss, Annette Wick reminds readers, caregivers and widows - We are not alone. We all share the common thread of struggling to live again. About the Author: Annette Januzzi Wick was born in northern Ohio and now lives in Cincinnati with her son and her newly blended family. Excerpts from I'll Be in the Car were awarded Honorable Mention in the 73rd Annual Writer's Digest Competition. I'll Be in the Car was awarded Finalist, Best Books 2006 Autobiography/Memoir.

Subject

Grief

Autologous CD22 CAR T cell Therapy for the Treatment of non-Hodgkin Lymphoma

CD19 targeting chimeric antigen receptor (CAR) T cell therapies (CAR19) are effective treatments for patients with non-Hodgkin Lymphoma (NHL), however, the majority of these patients will relapse. We have now evaluated a CD22 targeting CAR T cell therapy (CAR22) in patients who have large B cell lymphoma who have relapsed after CAR19 therapy and found that this therapy is both safe and effective resulting in a high rate of durable complete responses.

Clinical investigation to improve efficacy of CAR-T Cell Therapy for Large B Cell Lymphoma

We are investigating new interventions that could improve the effectiveness of CAR T-cell therapy for lymphoma. A clinical trial will test radiation immediately followed by CAR-T. Larger lymphoma tumors are less likely to respond to CAR-T and we expect that radiation could reduce the amount of tumor, leading to improvement in responses. We will also conduct a series of trials to determine the effectiveness of vaccinations before and after CAR T cell therapy, and if anti-cancer vaccines could improve outcomes.

Enhancing the “fitness” of anti-BCMA CAR T cells for improved efficacy in multiple myeloma

Chimeric antigen receptor (CAR) T cell therapy is a form of immune-based therapy where a patient’s own immune cells are genetically engineered to recognize and kill the tumor cells. This therapy has revolutionized the treatment of certain blood cancers and excitingly, two CAR T cell products were recently approved for the treatment of multiple myeloma.

Advances in Cancer Research and Treatment in 2020

Progress in new cancer treatments is accelerating so rapidly that the standard of care for many cancer patients is changing right before our very eyes.

Since 2017, the U.S. Food and Drug Administration (FDA) has approved a remarkable 53 therapies just to treat patients with blood cancers, and The Leukemia & Lymphoma Society (LLS) has helped advance 46 of these treatments.

I have no reason to believe the next few years won’t be as productive and groundbreaking as the last few. With that, here are some of my predictions for 2020:

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.

CLL-1 CAR-T cells and trametinib for the treatment of Ras-mutated CMML and JMML

We 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.

One Family’s Inspiring Quest to Help Other Families Impacted By Cancer

A nasty cough and extreme fatigue first led Myrna and Lou Binder to bring their 12-year-old son, Jeff, to the doctor for an examination. But the flu-like symptoms persisted until more tests enabled the doctors to arrive at the shocking diagnosis: non-Hodgkin lymphoma. The year was 1975.

Improving CAR-T cell therapy outcomes for patients with for aggressive lymphoma and multiple myeloma

Despite the promise of CAR-T cell immunotherapy for patients with lymphoma and multiple myeloma, a significant proportion of patients fail to respond or relapse following treatment. This project will focus on the clinical translation of a new treatment designed to improve durable response rates by combining CAR-T cell therapy with a new class of anticancer drugs called SMAC-mimetics. The results will provide the evidence base to drive a first-in-human clinical trial of this combination strategy.

CD70-directed CAR T-cell therapy for the treatment of relapsed/refractory pediatric AML

In this project, we will test an innovative therapy called CAR T-cell therapy for children with a type of cancer called AML. In the laboratory, we have identified and developed a powerful CAR T-cell therapy that targets a protein called CD70 on AML cells. We propose to now develop a clinical trial in which we will study the effects of this CD70.CAR T-cell therapy in children with AML.

BAFF-ligand CAR T-cells and pre-apheresis B cell lymphodepletion for relapsed / refractory CLL

Most CLL patients treated with CAR T-cells that target the CD19 antigen on the cell do not achieve a complete remission. CLL cells express other molecules on their surface; one of them is the receptor for BAFF (BAFF-R), which is highly expressed. We propose a phase I trial investigating LMY-920 for treatment of CLL. LMY-920 is a different type of CAR T-cell because it does not rely on an antibody structure to identify BAFF-R, but uses the structure of the ligand BAFF itself, and this may help avoid resistance to CAR T-cells.

TCR-like CARs targeting GvL mHAgs for the treatment of post-transplant AML relapse

AML recurrence is a devastating event after allo-HCT. I hypothesize that it could be counteracted through targeting of leukemia-restricted mHAgs via TCR-like CARs. I will identify scFVs recognizing mHAg:HLA complexes using a cell-free nanobody screening platform, and test the anti-leukemia activity and safety of CAR-Ts bearing such scFVs in vitro and in vivo. Through this approach, I will build a library of CAR constructs able to provide population-scale coverage for at-risk allo-HCT patients.

People with the most common type of blood cancer, chronic lymphocytic leukemia (CLL), are living longer than ever before without their disease progressing. While cures for CLL patients are still rare, survival rates have improved steadily over the last 50 years, with nearly 90 percent of people diagnosed with CLL today surviving at least five years, and most for many years longer.