April 1, 2017 | by City of Hope
City of Hope will highlight a variety of basic research and population studies at the annual meeting of the American Association for Cancer Research (AACR) at the Walter E. Washington Convention Center in Washington, D.C., April 1 to 5. The studies, presented by City of Hope physicians and researchers, could influence future approaches to drug-resistant cancers, treating aggressive brain cancers, recruiting diverse populations for research, and targeted therapies, among other advances.
“The AACR meeting is well-recognized as an important venue for sharing the most promising work being conducted in cancer research from many of the best and most accomplished physicians and scientists,” said Steven T. Rosen, City of Hope’s provost and chief scientific officer and director of Beckman Research Institute at City of Hope. “Basic and translational leading-edge cancer research being presented by City of Hope researchers and others helps share critical information that can lead to larger studies and ultimately advance better treatments for patients battling cancer.”
Among the research presented by City of Hope scientists will be symposiums and poster sessions outlining the results of four studies that address a variety of challenges in cancer treatment and research.
The highlighted presentations are:
CAR T cell cancer immunotherapy: Refinements for B cell malignancies and emerging opportunities in solid tumors
Christine Brown, Ph.D., the Heritage Provider Network Professor in Immunotherapy and associate director of the T Cell Therapeutics Research Laboratory at City of Hope, will be part of a major symposium discussing CAR T cell cancer immunotherapy on Wednesday, April 5, from 10:15 a.m. to 12 p.m. Brown will be focusing on the progress and challenges in CAR T cell therapy for aggressive brain tumors. In this type of therapy, T cells are isolated from a sample of the patient’s blood, then genetically engineered to seek out and attack a specific cancer. In 2016, Brown and others presented a case study that showed exceptional results in using CAR T cells to treat glioblastoma.
The session will be moderated by Michael C. Jensen, M.D., from Seattle Children’s Hospital and include Terry J. Fry, M.D., from the National Cancer Institute.
CD4+ outperform CD8+ central memory-derived CAR T cells, mediating persistent anti-tumor responses and long-term eradication of glioblastoma
Presented by third-year graduate student at City of Hope’s Irell & Manella Graduate School of Biological Sciences, Dongrui Wang, this talk will be part of a mini-symposium focused on “Adaptive Immunity in the Tumor Microenvironment” taking place on Monday, April 3, from 3 to 5 p.m.
Wang works in the lab of Brown and Stephen J. Forman, M.D., Francis & Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation, studying CAR T cell therapy as a way to treat glioblastoma, one of the most aggressive types of brain cancer.
For the work being presented at AACR, Wang and a team of City of Hope researchers compared two types of CAR T cells in mouse models to see how well each worked in attacking glioblastoma, with the eventual goal of optimizing CAR T treatments. The team found that CD4+ CAR T cells showed better anti-tumor activity over the CD8+ subset, as they were able to maintain long-term immune response and reduce stimulation-induced exhaustion. Therefore, they think that the frequency of CD4+ cells could be important criteria for evaluating the efficacy of CAR T cells as immunotherapeutic products for aggressive brain and other solid tumor cancers.
Partial knockdown of RLIP76 prevents cancer susceptibility of p53 null mice
Sharad S. Singhal, Ph.D., research professor in the Department of Molecular Medicine, will have findings presented during the “Chemoprevention and Cancer” poster session on Wednesday, April 5, from 8 a.m. to 12 p.m. His work, conducted with a team of scientists, examines the role of a transporter protein, RLIP76, in causing cancer.
Using mice who lacked p53 — a tumor suppressor whose functions appear to be lost or altered in nearly all tumor growth — the researchers tested the effects of RLIP76, which, when “knocked out,” or rendered ineffective in mouse models, results in protection from cancer. Singhal and colleagues reasoned that if RLIP76 is necessary for cancer to develop in p53-deficient animals, its suppression would reduce the incidence of malignancy in p53-deficient mice.
Their findings demonstrated that RLIP76 is required for malignancy in the mice lacking p53, meaning that the loss of p53 function alone does not cause cancer. The team’s previous studies have also found that mice without RLIP76 are highly resistant to inflammation and carcinogenesis in chemical carcinogenesis models of the skin and lung, so the present findings help to strengthen the rationale for using targeted systemic depletion of RLIP76 for treatment of human neoplasia.
Brassinolide, a plant steroid hormone, reverses drug resistance in human small cell lung carcinoma cells
Lung cancer research done by David Sadava, Ph.D., research professor, and Susan Kane, Ph.D., professor emeritus in the Department of Cancer Biology, will be presented as part of the “Basic and Applied Nanotechnologies and Therapeutic Approaches” poster session on Sunday, April 2, from 1 to 5 p.m.
Their work investigates the use of a plant steroid hormone in treating small cell lung carcinoma (SCLC), which has a particularly poor prognosis due, in part, to the fact that it is resistant to multiple drugs. But Sadava and Kane have found that a steroid hormone found in some plants can reverse resistance to certain chemotherapy drugs.
Epibrassinolide (EB), a natural product that can be found in abundance in certain plants, where its physiological effects are mediated via a similar pathway important to cancer development. EB was investigated by Sadava and Kane for its potential effects on lung cancer and was found to be toxic to drug-resistant SCLC cell lines, continuing to promote cell death over a 24-hour period. When paired with popular chemotherapy drugs, a synergy was seen between the two products that promoted efficacy of the drugs. The team’s data showed that EB is pharmacologically active in both drug-sensitive and drug-resistant SCLC cells, showing potential for widespread use in combining EB with drugs that SCLC cells typically resist to treat the disease.
Using community team science: An advocacy engaged approach to recruit ethnic minorities in cancer research
Results from community research led by Kimlin Ashing, Ph.D., professor and director of City of Hope’s Center of Community Alliance for Research & Education, will be presented as a late-breaking poster session on Monday, April 3, 8 a.m. to 12 p.m. This National Cancer Institute-funded project supported a team of researchers from City of Hope and community citizen scientists from the city of Duarte, Duarte Unified School District, Healthy Heritage and the Herald Cancer Association, who worked together to create a model for increasing community and provider responsiveness to increase minority engagement and participation in medical research at City of Hope.
To help evaluate their approach, the team implemented several aspects of their Partnered for Inclusion and Access in Research (PAIR) model among Latinas in the catchment area communities of City of Hope’s comprehensive cancer center. They formed a Community Advisory Council to serve as a community leadership resource. They collaborated with community partners on trainings and capacity-building for research-related engagement. A subgroup of the team created a video aimed to promote Latino participation in clinical trials, biospecimen studies and population-based research.
In one targeted effort, their multilevel approach resulted in the recruitment of 372 Latina women for biospecimen studies, representing 88 percent participation and demonstrating that the PAIR model is effective in engaging ethnic minorities in biomedical research. This approach can extend beyond City of Hope. In order to improve population health, medically underserved populations — such as ethnic minorities — ought to be represented in research to ensure optimal applicability and benefit of medical advancements for all.