Susanne Reyto, Chair
City of Hope’s Board of Governors
2003: Immunotherapy Focus on Brain Cancer
$150,000 - T-cell Therapy
T-cell therapy takes immune system cells from the patient and reprograms them through genetic engineering. The reprogrammed cells are then reintroduced into the patient's body. The expectation is that these T cells will kill only the tumor cells while leaving normal cells unharmed.
Our first Board of Governors grant provided the necessary funds for Michael Jensen, M.D., who is no longer at City of Hope, and Andrew Raubitschek, MD, chair of the Department of Cancer Immunotherapeutics and Tumor Immunology, to begin the first-in-human trial of reprogrammed T cells for glioblastoma, an aggressive form of brain cancer.
Currently, the T-cell trials are ongoing and show great promise in facilitating a cure for this devastating cancer.
2004/2005: Infrastructure to Support Clinical Trials
$500,000- Clinical lmmunobiology Correlative Studies Laboratory (CICSL)
$150,000 - Laboratory Specialist
In order to analyze the effectiveness of treatment during the clinical trials of glioblastoma patients, City of Hope needed a very sophisticated laboratory to investigate the precise and in-depth probing of a patient's immune system and responses during immunotherapy. Our grant established the Clinical Immunology Correlative Studies Laboratory (CICSL) with state-of-the-art equipment designed to do this precise analysis. An additional grant provided for a specialized laboratory supervisor needed to develop and implement additional analysis of immune cell functions and measure the status of the patient immune system during therapy. The CICSL is now a valuable shared resource doing analysis for several researchers in various fields of focus. The lab played a key role in the success of the neutral stem cell therapy of Karen Aboody', M.D. The lab has initiated a number of phase I and II clinical trials for glioma (brain tumor), B-cell lymphoma, relapsed non-Hodgkin lymphoma, acute lymphoblastic leukemia, acute myeloid leukemia, multiple myeloma and ovarian cancer. The lab's name has been changed to The Adoptive Cell Immunotherapy Laboratory.
2006: Research Into a Key Protein for Cancer
$150,000 - STAT3 Protein Study (Fast Track)
The STAT3 protein is found in almost all cells in our body. As a general rule STAT3 is dormant in normal cells. In contrast, STAT3 is constantly active in cancer cells and in the immune cells within and surrounding tumors. A team co-led by Hua Yu, Ph.D., now the Tim Nesvig Lymphoma Research Fellow at City of Hope, was the first to show that blocking STAT3 in tumors leads to tumor regression. Additionally, Yu, and her colleagues discovered that the active STAT3 protein strengthens the tumor cells while weakening the natural defense mounted by the immune cells around a tumor. By de-activating STAT3, Yu found that not only does the tumor cell die, but the surrounding immune cells regain their ability to fight cancer cells.
Our grant enabled Yu to focus on a “fast track” process where no government funding was available. With the results she established from our “seed money” she has been able to apply for and receive numerous major grants from the National Institutes of Health and others.
Currently, Dr Yu reports that significant progress has been made and she is very close to starting the first in-human trials. Her team has completed the necessary preclinical studies, optimizing the human version of the STAT 3 protein and are now producing quality STAT3 products to be used in clinical trials for the treatment of glioma and B cell lymphomas. These trials are scheduled to begin in October 2014.
2007: Clinical Research Advancement Fund
$500,000 - Fund Hiring Five Clinical Trial Physicians
The growth of the clinical trials program required an increase of doctors to treat and monitor patients in therapies being brought from the laboratory bench to the patient bedside. This grant was established to support the salary requirements for up to five doctors. These physician-researchers were specifically recruited to help design and then execute the phase I/II trials ready for in-human treatment. Initially three doctors were recruited in 2008 and at present our grant has allowed another five doctors to be recruited through 2012.
2009: Studies That Seek to Improve Care for Older Adults
$250,000 - Creating Geriatric-Specific Treatment Protocols
Arti Hurria, M.D., director of the Cancer and Aging Research Program, concentrates her research on cancer in the aging population and developing more patient-friendly treatments. Our grant was to provide the funds for a study of the effects of chemotherapy in the older population.
Her research to identify risk factors for severe chemotherapy side effects in older adults enrolled 500 patients from seven participating institutions across the U.S. The results of the study were published in the Journal of Clinical Oncology in 2011 and was identified by the American Society of Clinical Oncology as one of the “Clinical Cancer Advances in 2012.”
A similar study was initiated by her team, specifically for older women with breast cancer. Based upon the results of her first study, the National Institute of Health recently awarded Hurria a $2.5 million grant, with additional funding support from the Breast Cancer Research Foundation,
In 2013 she was recognized by the American Society of Clinical Oncology with the B.J. Kennedy award for scientific excellence in geriatric oncology.
2011: Targeting the Mechanism Behind Cancer's Growth
$250,000 - Attacking the DNA That Replicates Cancer Cells
Linda Malkas, Ph.D., deputy director of basic research and professor in the Department of Molecular and Cellular Biology, has discovered a key protein within a breast cancer cell that replicates the cell and creates a tumor mutation which continues to copy. She has identified six agents (out of more than 6 million tested) that inhibit this protein from reproducing - thereby stopping the cancer in its tracks. She is also collaborating with Hua Yu, Ph.D., our 2006 grant recipient. Malkas believes the BOG grant will give her the needed funds to bring her research from the bench to the bedside and begin the first-in-human trial of her protocol within two years.
UPDATE: Neuroblastoma is one of the most common childhood neoplasms, brain cancer. Her team previously reported a novel cancer which was significantly expressed in a broad range of cancer cells, but not in nonmalignant cells. Malkas and her research team designed a molecule to test this hypothesis. Their investigation shows that this molecule selectively kills human neuroblastoma cells with very little toxicity to nonmalignant cells. They are working with pediatric oncologists to conduct pre-clinical testing.
2013: Merging of Eastern and Western Medicine
$100,000 - Using natural compounds found in Traditional Asian Medicine
John Hosei Yim, M.D., associate professor of surgery, performs breast and endocrine surgery, and conducts research for breast and endocrine cancer treatments. Yim works with natural compounds found in traditional Asian medicine, as well as superfoods such as blueberries, mushrooms, and soy. His laboratory has discovered a compound found in a Chinese root, baicalein, which activates a protein that causes cancer cells to kill themselves and makes them more susceptible to our immune systems. It can also inhibit cancer cell growth in glandular tissue including breast, prostate, ovary and even colon. According to his studies, tumors can shrink in mouse models, including those that are resistant to chemotherapy. Yim's therapy can combine with chemotherapy to shrink tumors even further, while lessening the toxicity of the chemotherapy.
This compound will be given orally. City of Hope has a pharmaceutical plant on the campus that will manufacture the clinical grade baicalein pills which will eventually be given to patients being treated at City of Hope. The support from the BOG will provide the funds needed to manufacture these pills and allow for studies to confirm its safety and efficacy in tumor bearing mice, in preparation for Food and Drug Administration approval for clinical trials. The results of these studies will provide the foundation for further funding from the National Institute of Health or other organizations for merging Eastern and Western Medicine, which hopefully will result in more effective, less toxic, and perhaps even preventative treatments for cancer patients.
2013: The Smart Bomb Approach to Curing HIV/AIDS
$100,000 -- BioRad QX100 Droplet Digital PCR instrument
John Rossi, Ph.D., professor, Molecular and Cellular Biology, and John C. Burnett, Ph.D., assistant research professor, Molecular and Cellular Biology, will be using this instrument to measure the levels of cancer markers and to test new therapeutics which may reduce the levels of cancer cells.
With the help of this highly precise measuring device, that gives exponential amplification of nucleic acids, using their new gene editing technology, CRISPR, they will target HIV genes in infected cells. The doctors have engineered biological molecules to deliver the therapeutics only to the intended cells and devised methods to target only the HIV genes without affecting the human genes. This greatly reduces toxicity. These strategies mark a highly specific and potent approach for eradicating HIV.
Importantly, CRISPR technology will also be applicable for many types of cancers and other genetic diseases. It will also be used to develop new anti-cancer agents currently under investigation for pancreatic cancer, B-cell lymphoma, and T-cell leukemia.
According to Burnett, to his knowledge, no one has ever used this instrument to discover these new agents and he is preparing a patent application for this purpose making this instrument the focal point of a breakthrough technology.
Their findings will confirm that the agents can eradicate cancer and HIV in animal models. These important initial experiments will enable City of Hope to secure federal funding and prepare for the most critical step, human clinical trials with new therapeutics.
The following doctors have all benefited from the Board of Governors grants towards their research. Their area of expertise covers cancer, immunotherapeutics, tumor immunology, surgery, oncology, hematology, neurological spine, hematopoietic cell transplantation and molecular/cellular biology.
Saro Armenian, D.O, M.P.H., John C Burnett, Ph.D., Robert Figlin, M.D., F.A.C.P. (no longer at City of Hope), Stephen Forman, M.D., Julio Garcia-Aguilar, M.D., Ph.D., Ernest S. Han, M.D., Ph.D., Arti Hurria, M.D., Ruhal Jandial, M.D., Ph.D., Michael Jensen, M.D. (no longer at City o.f Hope), Michael Kalos, Ph.D. (no longer at City of Hope), Theodore G. Krontiris, M.D., Laura Kruper, M.D., Linda Malkas, Ph.D.