Researchers at City of Hope will present late-breaking clinical trial findings at this year's American Association for Cancer Research Annual Meeting, which begins April 8. These additional presentations showcase a pilot program in tobacco use cessation and new developments in cell therapy.
Engineering natural killer cells
Jianhua Yu, Ph.D., a professor in the Department of Hematology & Hematopoietic Cell Transplantation, Michael Caligiuri, M.D., president of City of Hope National Medical Center and the Deana and Steve Campbell Physician-in-Chief Distinguished Chair, and colleagues have developed a new cell therapy approach using natural killer cells that, in lab models, induced a greater response against acute myeloid leukemia (AML) and lengthened the survival of mice with AML without damaging healthy blood stem cells. The treatment could one day provide a viable cell therapy option for patients with AML, who traditionally have not benefited from innovative cell therapy treatments. When these patients experience relapse, it often occurs rapidly, so there is not enough time to prepare patient-derived chimeric antigen receptor (CAR) T cell therapy. City of Hope researchers believe the off-the-shelf cord blood approach they are developing will provide a breakthrough treatment option for a subpopulation of AML patients with the FLT3 gene.
Ting Lu, Yu, Caligiuri and colleagues have engineered off-the-shelf natural killer cells to make a protein that causes them to be 10 times more potent in killing human lung cancer cells grown in the lab. When tested in mice transplanted with human nonsmall cell lung cancer, the innovative cell therapy City of Hope developed worked better than unengineered natural killer cells and did not appear to affect body weight, liver or kidney function, or blood counts, suggesting a safe and effective approach to test clinically.
The team will present their data in two poster presentations on Monday, April 11, and Wednesday, April 13.
oncolytic virus Plus CAR T cell therapy
Christine Brown, Ph.D., The Heritage Provider Network Professor in Immunotherapy and deputy director of the T Cell Therapeutics Research Laboratory, will present data to support the initiation of a Phase 1 clinical trial combining CAR T cell therapy with a cancer-killing oncolytic viral therapy for the treatment of recurrent glioblastoma. This combination trial builds on interim clinical findings from City of Hope and the University of Alabama at Birmingham (UAB). A CAR T cell therapy Phase 1 trial being carried out at City of Hope for recurrent glioblastoma suggests that the more immune cells within the tumor, the longer the patient’s survival. The oncolytic viral clinical Phase 1 trial conducted by UAB used an oncolytic virus engineered for improved gene expression and viral replication to kill specific brain tumor cells; early findings suggest that the virus could activate immune responses in the brain. Based on these human clinical trials, the research team treated mice with brain tumors first with the oncolytic virus, then with cell therapy, and showed that together the two treatments did not cause any side effects. Based on these findings, a clinical trial under a Mustang Bio investigational new drug application will soon open to try this combination on two types of brain tumors. The team will share their findings in a poster presentation on Wednesday, April 13.
Empowering patients to quit smoking
Cary Presant, M.D., professor in the Department of Medical Oncology & Therapeutics Research, Kimlin Tam Ashing, Ph.D., professor in the Department of Population Sciences, and Steven Rosen, provost, chief scientific officer and the Irell & Manella Cancer Center Director's Distinguished Chair, and colleagues developed a novel Personal Pathway to Success program where cancer patients were able to choose from 27 individualized tobacco cessation services to help them quit smoking prior to surgery. The pilot program was offered to 54 patients in a preoperative anesthesia testing clinic, and 23 completed counseling. The availability of the program increased initial patient interest from less than 10% to more than 50% of patients working to quit smoking. The innovative, personalized intervention program appears to be effective, partially because it reaches cancer patients during presurgery visits, when they seem to be more receptive to a “teachable moment” of behavioral changes to prevent disease. The team will share their findings in a poster presentation on Friday, April 8.