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Towards clinical testing of epitope editing to enable novel adoptive immunotherapies

Innovations in gene engineering have made it possible to reprogram immune cells to attack specific targets on cancer cells, allowing the first adoptive cellular immunotherapies, known as CAR T cells, to be approved by the FDA for the treatment B lymphoblastic leukemia. A similar approach is currently under development for AML, but in contrast to B-ALL, there is no leukemia-specific target which would be amenable to targeting by immune cells without incurring severe adverse effects.

T cell Memory in Cure of Diffuse Large B Cell Lymphoma: An Investigation of the Immune Interactome

While many patients with diffuse large B cell lymphoma (DLBCL) are cured with initial treatment, some patients relapse even after multiple therapies, and their outcomes are poor; we believe that the quality of the patient’s T cell memory plays a critical role in determining how they respond to treatment. To investigate, we will analyze the response pattern of circulating immune cells in cured and relapsed DLBCL patients, as well as the immune signals generated by the tumors, and create CAR T cells from the T cells with anti-tumor properties found in cured patients.
larry

Larry

Larry Loose, a great big bear of a man with a penchant for classic cars, off road racing, dirt bikes and living large. This man, my husband of twenty five years, had worked 12-hour days for decades in hopes of being able to retire early, move to the desert and spend our later years as snowbirds in beautiful Arizona.

leukemia

Greg

Today I am a proud dad, avid skier, business owner and husband. For a moment though, let’s flash back to college. I wasn’t feeling well but I needed to take one last final just before winter break. After the final, I went to the school clinic and the next thing I knew it was January and I was in a hospital bed in Denver.

I was 19 years old and had been flown in a helicopter from my college town of Durango, CO to Denver. I had been in an induced coma for the last three and a half weeks. I woke up unable to speak or move my arms, legs - I couldn’t even lift a finger.

Paul

Paul

Thank you on behalf of the Freeman Wilner Family for this Honored Hero Award in memory of my father, Dr. Freeman Wilner, he was a hero to many.

Hollis

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.

Douglas

My story begins almost 24 years ago in 1996, when I was diagnosed with cancer, chronic lymphocytic leukemia (CLL). Back then, there was no cure for CLL except for a bone marrow transplant (BMT), but that procedure only had a survival rate of 50%, not very attractive odds. My prognosis was I had anywhere from six to 15 years without a BMT.

hazy photo of middle-aged woman with blond hair gray eyeshadown pink lipstick and gold earrings and necklace in a black dress

Rebecca

My mother died of multiple myeloma (MM) in 2001, 10 months after her diagnosis. She lived in a small town where the only treatment they offered her was chemo infusions. She was on dialysis the whole time. She was brave but scared, nonetheless. She didn't have much time to process the whole experience. I was 51 at the time and still believed I was bullet-proof! Silly girl!

Improving targeted adoptive cell therapy of myeloma

Dr. Madhav Dhodapkar, M.D., of Winship Cancer Institute of Emory University, Atlanta, leads a multi-institutional, multi-disciplinary LLS Specialized Center of Research team focused on advancing new immunotherapies for patients with multiple myeloma. Their goal is to improve the effectiveness of CAR T-cell immunotherapy, which engineers the patient’s T cells to find and kill cancer cells. The CAR-T they are studying targets a protein called BCMA found on the surface of all myeloma cells.

Immunotherapy

Immunotherapy uses your own immune system to fight cancer. There are several types of immunotherapies, and each works to help the immune system in a different way. Some boost your body’s immune system. Others train your immune system to attack specific cancer cells.

Immunotherapies being used or studied to treat blood cancer include:

smiling middle aged white man with graying hair and mustache wearing a brown jacket and blue shirt

Todd

I was diagnosed at age 33 as a result of an unrelated blood test, very young, I was told. Fluorescence in situ hybridization (FISH) showed low risk. My local oncologist sent me to a regional teaching hospital to get a second opinion, and that opinion was, "If I had to pick a cancer, this would be it." Terrible start!

Chemotherapy and Drug Therapy

The main treatment for active myeloma is systemic drug therapy (meaning the drugs travel through the bloodstream to kill malignant cells). The initial therapy, or “induction therapy,” for myeloma usually includes a combination of targeted agents and/or standard chemotherapy. This therapy is often followed by stem cell transplantation in eligible patients.

Common drugs combinations for people with newly diagnosed myeloma include:

Pharmacological strategies to enhance T- and NK-cell-based therapies in blood cancers

Although they represent a major therapeutic progress for blood cancers, CAR-T cells and other T-cell based therapies are subject to eventual development of resistance to many patients. Natural killer (NK) cell-based therapies are highly active against many types of blood cancer cells which are resistant to T cells, but in our CRISPR studies death receptor signaling defects emerge as a common downstream mechanism of resistance to both T- and NK-cell therapies.
Allyson

Allyson

In November 2016 I was tired. TIRED. I had a 20-month-old and a 4-year-old, had just come off the busiest month of the year for work, and I figured I was tired for no other reason. But then tired became not having the energy to take care of my 20-month-old. Tired became going to be my best friend's wedding and needing to lay down in between steps. Shower, lay down. Makeup, lay down. Hair, lay down. Get dressed, sit for a minute. Walking a long hallway seemed daunting. And then carrying my son from my car at a gas station to the restroom inside on a road trip was too much.

Zach stage 3 Hodgkin lymphoma (HL)

Zach

It was 2020, and besides the obvious chaos in the world, at that time my life was going great. My business was thriving, I had just gotten engaged, and my fiancée and I were beginning to talk about starting a family. I was at what felt like the peak of my life. Everything was going my way, or so I thought.

Immunotherapeutic Targeting of FCRL1 in CLL

Evolving insights into the B cell-restricted FCRL1 surface protein reveal that it integrates with critical signaling pathways and is a promising immunotherapeutic target in CLL. Based on preclinical evaluation of novel FCRL1 monoclonal antibodies, we propose developing chimeric antigen receptor (CAR) T cells for targeting in unique mouse models and patient-derived cells. The results will form the basis for strategic drug development and clinical testing in CLL and related B cell malignancies.

T cells with native and chimeric receptors against multiple tumor targets for acute myeloid leukemia

Adoptive T cell therapies for acute myeloid leukemia face numerous hurdles such as limited target antigens, immunosuppressive tumor environment as well as the loss of efficacy due to downregulation of the targeted antigen. The goal of our project is to address some of these challenges with a single T cell product targeting multiple tumor associated antigens that have limited expression on healthy tissues via a novel combination of native T cell receptor and gene engineered CAR targeting.
stage IV Hodgkin lymphoma (HL)

Elisa

I was diagnosed with stage IV Hodgkin lymphoma (HL) in April 2022 at 27 years old. After months of debilitating symptoms and a week-long hospital stay, I finally had an answer as to what was going on with my body. I was relieved to have an answer, but "cancer" was the last thing I expected. Ironically, after my diagnosis and first chemotherapy infusion, I felt better than I had in months. I didn't feel like I had cancer; the only reminders were a few enlarged lymph nodes and the mediport protruding from the right side of my chest. 

leukemia

Austin

Four were spoken that day. Four crushing, breathtaking words, “Your son has cancer.” My world, my life, and my dreams for my son’s future suddenly halted while the rest of the world kept going on around us on May 14, 2011. Only days before, I was deciding what theme to have for his third birthday party and what outfit he would wear for his pictures. Days later, my husband and I were signing consents for the specific protocol of poison that would be pumped into Austin and having to digest the laundry list of possible side effects.

Rylie

Rylie

My name is Rylie York, I am 20 years old and I'm currently a sophomore at Baylor University. I'm originally from Round Rock, Texas and I am a patient at Texas Children's Hospital in Houston, Texas. I was diagnosed with stage 4 Hodgkin’s lymphoma at 18 in the middle of my senior year of high school. I have relapsed twice since then and completed my bone marrow transplant this past August and September.

WG

Will

I am a cancer mom. I WAS a cancer mom. My youngest son, Will, was diagnosed with Hodgkin lymphoma (HL) at age 19 in April of 2019. He, his dad, and I were beyond shocked when we heard the news that the swollen lymph nodes that came up out of the blue one March morning were indeed HL. We didn't really know anybody personally that had it. We didn't know what exactly all the words meant at that moment in time, but we knew it wasn't what we had planned for our youngest son.

Targeting the cell surface U5 snRNP complex as a novel immunotherapy for AML

A major limitation of immunotherapy approaches for AML has been the lack of known targetable cell surface antigens specific to AML cells. This project characterizes the pathologic and biologic effects of a novel cell surface antigen complex uniquely present on AML cells but not normal hematopoietic precursors, known as the U5 snRNP complex. Furthermore, we will interrogates U5 snRNP complex components as novel AML-associated antigens and CAR T cells targets for AML treatment.

Precision Medicine Inhibitor and Immunotherapy Approaches for High-Risk Childhood Leukemias

Dr Tasian’s scientific passion is successful development of precision medicine therapies for high-risk childhood leukemia. Her translational laboratory research program focuses upon investigation of kinase inhibitors and chimeric antigen receptor (CAR) T cell immunotherapies in childhood ALL and AML using primary patient specimens and patient-derived xenograft models. Through her laboratory and clinical research, she aspires to improve cure rates and minimize toxicities for children with leukemia.
Elisabeth

Elisabeth

I was first diagnosed at 12 years old when I didn’t even know what the word cancer meant. I remember sitting at the kitchen table with my family, laying my head down and sobbing because they told me I would lose my hair. I have lost my hair five times since. You see, fighting tooth and nail for your life at a young age produces a certain type of grit ― one where you choose daily to do hard things while also stopping to smell the flowers on the way, one where you enjoy the little moments most take for granted because tomorrows were never promised.