City of Hope researchers to present latest cell therapy and precision medicine advances at AACR

LOS ANGELES — Researchers at City of Hope, one of the largest cancer research and treatment organizations in the United States, will present a number of new findings at this year’s American Association for Cancer Research Annual Meeting, which will take place April 8 to 13.

 

 

“Regional administration of IL-12 endowed CAR T cells effectively targets systemic disease”

Eric Lee and Saul Priceman have developed a second-generation CAR T cell product targeting a tumor-associated antigen, TAG72, that, when tested in mice with ovarian tumors, largely overcame the barriers that limit CAR T cell therapy from working in solid tumors. Additionally, they engineered these CAR T cells to produce a cytokine that further enhanced their activity in vivo. These modifications lend hope that soon CAR T cell therapy can overcome the immunosuppressive tumor microenvironment and be used to treat more types of cancers. The researchers will soon start recruiting patients for a phase 1 clinical trial testing the TAG72-CAR T cell product in women with ovarian cancer.

 

“A mathematical model for optimization of combination therapy involving targeted radionuclide and CAR T cell therapy”

Vikram Adhikarla and Russell Rockne led preclinical research that treated mice with multiple myeloma with CAR T and targeted radionucleotide therapy to develop a mathematical model and optimize combination therapy delivery. By varying the length of time between treatments, they found that the rate of tumor growth had the most impact on treatment success.

 

 

“The N⁶-methyladenosine reader YTHDC1 is essential for TGF-beta-mediated metastasis of triple negative breast cancer”

Brandon Tan, Jianjun Chen and colleagues have discovered a gene that, when removed from triple-negative breast cancer cells grown in a dish, also removes their ability to move and metastasize, suggesting that its normal role promotes cancer spread. The research team was able to uncover that this gene promotes metastasis by increasing the activity of a molecular chain of events that is common to many different cell functions.

 

“The impact of carcinogens, obesity and chronic inflammatory processes on mutational signatures and cancer risk in mouse tumor models”

An estimated 40% of all human cancers are suspected to be a result of modifiable risk factors, such as obesity, high-fat diet and chronic inflammation; however, whether genomic signatures exist for modifiable cancer risk factors remains. Yun Rose Li and colleagues report the analysis of nearly 300 mouse tumors using multiple models of human cancers in the setting of obesity, high-fat diet, wounding, chronic inflammation or chemotherapy to evaluate their impact on the cancer genome. They found that these factors are critical in controlling when tumors develop, and thus behaviors and environment impact cancer susceptibility and development. In combination with recently published work in the journal Nature Genetics on the impact of suspected environmental carcinogens in eliciting tumors in mice, the present study represents the largest compendium of whole genome sequencing data from nearly 300 mouse tumors, offering important insights on how cancers arise and the critical impact of behavior and environment in tumor development.

 

“METTL16 drives leukemogenesis and maintains leukemia stem cell self-renewal via reprogramming BCAA metabolism”

Li Han, Jianjun Chen and colleagues have found that removing an RNA-modification enzyme from acute myeloid leukemia cells in mice slowed acute myeloid leukemia progression and practically stops leukemia stem cells from dividing, making this enzyme an attractive target for designing new drugs/treatments for AML.

 

“An exosomal miRNA-based liquid biopsy signature for the noninvasive early detection of pancreatic ductal adenocarcinoma”

Ajay Goel and colleagues have identified a new marker for pancreatic ductal adenocarcinoma that identifies with accuracy higher than the typical biomarkers currently used. With more research, this biomarker could greatly improve outcomes for pancreatic cancer patients who have a condition that is typically diagnosed so late that only 20% of cases are operable.

 

“Predicting response to chemotherapy in a mouse model of acute myeloid leukemia”

Lisa Uechi, Russell Rockne and colleagues developed a mathematical model to illustrate how blood cells go from healthy to progressive states of acute myeloid leukemia. Using mice with AML, they followed which genes are turned on and off over the course of the disease, extending their mathematical model to predict how AML responds to chemotherapy and when relapse likely will occur. An ability to accurately predict treatment response and disease relapse could help treatment timing and strategies and possibly improve outcomes.

 

“Accelerated biological age is a driver of cancer susceptibility in genetic high risk breast tissue”

Mark LaBarge and colleagues found that women with underlying genetic susceptibility for breast cancer show indications of faster aging in their breast tissue, with some cells appearing 40 years older than the woman herself. This work identifies markers that link breast cell age and cancer risk independent of the patient’s genetic background, age or cancer subtype.

 

City of Hope's mission is to deliver the cures of tomorrow to the people who need them today. Founded in 1913, City of Hope has grown into one of the largest cancer research and treatment organizations in the U.S. and one of the leading research centers for diabetes and other life-threatening illnesses. As an independent, National Cancer Institute-designated comprehensive cancer center, City of Hope brings a uniquely integrated model to patients, spanning cancer care, research and development, academics and training, and innovation initiatives. Research and technology developed at City of Hope has been the basis for numerous breakthrough cancer medicines, as well as human synthetic insulin and monoclonal antibodies. A leader in bone marrow transplantation and immunotherapy, such as CAR T cell therapy, City of Hope’s personalized treatment protocols help advance cancer care throughout the world.

 

With a goal of expanding access to the latest discoveries and leading-edge care to more patients, families and communities, City of Hope’s growing national system includes its main Los Angeles campus, a network of clinical care locations across Southern California, a new cancer center in Orange County, California, scheduled to open in 2022, and Cancer Treatment Centers of America. City of Hope’s affiliated family of organizations includes Translational Genomics Research Institute and AccessHope^TM. For more information about City of Hope, follow us on Facebook, Twitter, YouTube, Instagram and LinkedIn.