City of Hope scientists present latest cancer research advances at AACR

Eric Lee, B.S., research associate, and Saul Priceman, Ph.D., assistant professor and associate director of Translational Sciences & Technologies in the T Cell Therapeutics Research Laboratory at City of Hope, 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. They will present their findings in a poster presentation on Sunday, April 10.

Vikram Adhikarla, Ph.D., assistant research professor, and Russell Rockne, Ph.D., associate professor, in the Department of Computational and Quantitative Medicine within Beckman Research Institute of City of Hope, 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.They will present their findings during a poster session on Tuesday, April 12.

Brandon Tan, Ph.D., a postdoctoral fellow in the Department of Systems Biology at City of Hope, Jianjun Chen, Ph.D., professor and Simms/Mann Family Foundation Chair in Systems Biology, 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. They will present their findings during an oral minisymposium on Monday, April 11.

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, M.D., Ph.D., assistant professor in the departments of Radiation Oncology and Clinical Genetics and Epigenetics at City of Hope, 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. They will present their findings during an oral minisymposium on Monday, April 11. 

Li Han, Ph.D., postdoctoral fellow in the Department of Systems Biology at City of Hope, Jianjun Chen, Ph.D., 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 and treatments for AML. They will present their findings in an oral minisymposium on Tuesday, April 12. 

Kota Nakamura, M.D., Ph.D., visiting scholar, Ajay Goel, Ph.D., M.S., professor and chair, Department of Molecular Diagnostics and Experimental Therapeutics and associate director of basic science at City of Hope,
and colleagues have identified a new marker for pancreatic ductal adenocarcinoma that identifies the disease 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. They will present their findings during a poster presentation on Tuesday, April 12. 

Lisa Uechi, Ph.D., postdoctoral fellow in the Division of Mathematical Oncology in the Department of Computational and Quantitative Medicine at City of Hope, Russell Rockne, Ph.D., 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. They will present their findings in a poster presentation beginning Friday, April 8.

Mark LaBarge, Ph.D., professor in the Department of Population Sciences at City of Hope, 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. They will present their findings in a poster presentation beginning Friday, April 8.