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City of Hope Researchers Present Breakthrough Findings at AACR 2021

City of Hope will showcase breakthrough research and innovative studies at the first week of the American Association for Cancer Research (AACR) Annual Meeting 2021, which will take place virtually from April 10 to 15.
City of Hope scientists will present findings that could one day lead to an effective KRAS inhibitor for solid tumors, innovative chimeric antigen receptor (CAR) T cell therapy for glioblastoma, potent CAR natural killer cell therapy against pancreatic cancer, improved health equity for marginalized communities, better ways to prevent and treat colorectal cancer, and much more.
The multidisciplinary meeting program will highlight the best cancer science and medicine in the world. Last year, more than 73,000 people from 140 countries attended AACR’s first-ever virtual meeting. Some City of Hope research that will be presented at the AACR meeting is highlighted below.

New Targeted Treatment Options for Solid Tumors

This late-breaking oral presentation led by City of Hope’s Marianna Koczywas, M.D., clinical professor in the Department of Medical Oncology & Therapeutics Research, will address the anti-tumor activity and tolerability of the SHP2 inhibitor RMC-4630 as a single agent in patients with RAS-addicted solid cancers. The first-in-
Marianna Koczywas, M.D.
human Phase 1 study demonstrated that RMC-4630 is a potent, selective inhibitor of SHP2, which appears to be an important regulator of growth signals for cancer cells. RMC-4630 exhibited anti-tumor activity in cancers harboring KRASG12C, KRASG12D, NF1 loss of function and BRAF Class 3 mutations. Based on these findings, four targeted therapy combination studies are currently underway, including combinations of RMC-4630 with the KRASG12C inhibitor sotorasib, the checkpoint inhibitor pembrolizumab and the MEK inhibitor cobimetinib.

CAR T Cell Therapy for Glioblastoma

This translational research evaluates how CAR T cell therapy reshapes the tumor microenvironment to promote host anti-tumor immune responses in glioblastoma. Christine Brown, Ph.D., The Heritage Provider Network
Christine Brown Bio
Christine Brown, Ph.D.
Professor in Immunotherapy and deputy director of the T Cell Therapeutics Research Laboratory at City of Hope, and her colleagues look at IL13Rα2-targeted CAR T cells for the treatment of glioblastoma and demonstrate that CAR T cell treatment of mice with glioblastoma alters the tumor immune landscape, activates myeloid cells within tumors and induces innate T cell memory responses. These studies establish that CAR T cell therapy has the potential to reshape the microenvironment of solid tumors, potentially activating innate, adaptive immunity. Cancer Discovery recently accepted the manuscript for publication.

CAR NK Therapy for Pancreatic Cancer

This late-breaking poster presentation led by City of Hope’s Michael Caligiuri, M.D., the Deana and Steve Campbell Physician-in-Chief Distinguished Chair, and Jianhua Yu, Ph.D., director of the Natural Killer (NK) Cell
Michael Caligiuri
Michael Caligiuri, M.D.
Biology Research Program, presents a potent human CAR NK cell therapy against pancreatic cancer. About 60-80% of pancreatic cancers express prostate stem cell antigen. The scientists developed CYTO NK-203 to spontaneously kill both liquid and solid tumors in animal models using human umbilical cord NK cells that are transduced with CAR. The research suggests that this biopharmaceutical may be able to prolong survival against pancreatic tumor cells without side effects, at least in animal models. CYTO NK-203, which was licensed to CytoImmune Therapeutics Inc., is expected to move into clinical trials at City of Hope within 12 months, Caligiuri said.

Neighborhood Disadvantage Linked to Aggressive Lung Cancer

City of Hope’s Loretta Erhunmwunsee, M.D., assistant professor in the Division of Thoracic Surgery, looked at the association of neighborhood disadvantage and the biology of aggressive nonsmall cell lung cancer. Nonsmall cell lung cancer has a disproportionately higher incidence and mortality rate in marginalized
Doctor Loretta Erhunmwunsee
Loretta Erhunmwunsee, M.D.
communities, who often reside in neighborhoods with adverse conditions influenced by economic, housing, education, transportation and environmental factors. Researchers looked at 426 nonsmall cell lung cancer patients treated at City of Hope and found that those who lived in disadvantaged neighborhoods were more likely to have a somatic KRAS mutation — a mutation that is associated with lower survival. This relationship was consistent even when smoking status and pollution were considered and suggests neighborhood disadvantage may be an important determinate of aggressive nonsmall cell lung cancer biology, possibly explaining why marginalized individuals have worse outcomes.

Predictors of Immune Responses in Colorectal Cancer

Stephen Gruber, M.D., Ph.D., M.P.H., director of City of Hope’s Center for Precision Medicine, studied clinical and epidemiologic predictors of clonal immune responses in colorectal cancer to better understand what causes diverse immune responses. He and his colleagues found that the use of statins and daily aspirin for more than
Stephen Gruber
Stephen Gruber, M.D., Ph.D., M.P.H.
five years prior to when a patient was diagnosed with colon cancer was strongly associated with the quality and behavior of the immune cells (T cells) within the tumor itself. Their research suggests that adaptive immune response may be linked to modifiable factors. Having a better understanding of the mechanisms that regulate immune responses in colorectal cancer may have implications for chemoprevention and immunotherapy.