Scientists from the Fred Hutchinson Cancer Research Center in Seattle are scheduled to present and discuss the latest developments in immunotherapy and proteomics at the American Association for Cancer Research Annual Meeting, Research Propelling Cancer Prevention and Cures, on April 1-5. What follows is a selection of the more than 30 Hutch presentations at the AACR gathering.
Developing adoptive T-cell therapy for ovarian cancer
Dr. Kristin Anderson, a postdoctoral fellow in Dr. Philip Greenberg's lab at Fred Hutch, will present findings on a new adoptive T-cell therapy for ovarian cancer, a type of solid tumor with a very low survival rate among women and few new treatment options. Anderson and her colleagues engineered T cells to recognize a protein overproduced on these cancer cells, and then tested the therapy on human ovarian cancer cells in the lab and in a mouse model of ovarian cancer. The findings showed that the T cells killed human ovarian cancer cells and that the treatment extended the mice's survival. But the research also highlighted how the tumor microenvironment of ovarian cancer presents unique challenges to the therapy. She and her colleagues have identified several roadblocks to T-cell therapy that are unique to solid tumors (as compared with blood cancers, where T-cell therapy is farther toward clinical benefit) and will present strategies underway in the Greenberg lab to overcome those roadblocks with new therapies. Anderson is speaking April 4 at 3:50 p.m. Her talk is titled, "Engineering adoptive T-cell therapy for efficacy in ovarian cancer."
Beyond genomics: Using proteomics to target tumors
From the Human Genome Project onward, we've made a massive investment in science aimed at understanding human genomics. But there's a problem: Proteins, not genes, do most of the work of our cells and are the targets for most of our medicines -- and there's no standardized, reliable way to measure the vast majority of proteins in our bodies. Into this black hole steps Dr. Amanda Paulovich, an oncologist and cancer geneticist at Fred Hutch. She and her team are developing new technologies and assays for accurately measuring levels of proteins that could finally retire the prevailing technology in use for the last 50 years. The methods she and collaborators have developed are poised to make the genome actionable for patients at last by opening a window into the missing biology of our proteome. Paulovich, whose lab was recently tapped by the Cancer Moonshot to identify new tumor markers using advanced proteomics, will speak April 5 at 10:20 a.m. Her lecture is titled, "Translational mass spectrometry: Making the genome actionable for cancer patients."
Vaccine adjuvant boosts immune response to sarcomas
An experimental drug based on a molecule in the bacterial cell wall can stimulate an immune response in advanced tumors, a Fred Hutch-led research team found in a small, early phase study in patients with metastatic soft-tissue sarcomas. After injecting the drug (called G100) into tumors just underneath the skin, Dr. Seth Pollack, an assistant member in the Hutch's clinical research division, and his colleagues observed signs of heightened immune activity in the treated tumors. G100 is used as an immune stimulator, or adjuvant, in experimental anti-cancer vaccines, and similar compounds are part of FDA-approved vaccines for HPV and hepatitis B. The growth of the treated tumors was controlled after injection in 14 of 15 participants, and one participant's injected tumor completely regressed. The researchers are now designing a new trial that would combine G100 injections with a systemic immunotherapy, with the aim of stimulating an anti-cancer response throughout the body. Dr. Yongwoo Seo, a Fred Hutch research fellow and surgery resident at the University of Washington, will present the findings April 3 from 1- 5 p.m during a poster session, "Intratumoral injection of the toll-like receptor 4 agonist G100 induces a T-cell response in the soft tissue sarcoma microenvironment." For additional background on sarcomas and immunotherapy, view this video of Dr. Pollack: https:/
Expert sources on immunotherapy
Fred Hutch is pioneering new immunotherapies and has played a leading role in advancing our understanding of how the immune system can be harnessed to fight cancer. The following Hutch researchers will be speaking at AACR and can provide comment on developments and challenges in the field:
- Dr. Phil Greenberg, one of the two editors-in-chief of AACR's Cancer Immunology Research, will be speaking April 3 at 4 p.m. in a "Meet the Editors" session about the journal and the scope and type of research articles it is seeking in the coming year. Greenberg, who is head of the Program in Immunology at Fred Hutch, led some of the earliest studies showing how T cells can recognize and eliminate malignant cancer cells and developed technologies to isolate and expand functional, target (antigen)-specific T cells to numbers large enough to be effective when given to patients as adoptive immune-boosting therapy. He is a professor of immunology and medicine at the University of Washington and was elected this spring to AACR's board of directors. Here's a video of Dr. Greenberg on the new era of cancer research: https:/
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- Dr. Stanley Riddell, director of the Immunotherapy Integrated Research Center at Fred Hutch and a pioneer in the development of CAR T-cell therapy, will deliver a talk, "Understanding success and failure of T-cell therapy for B-cell malignancies," on April 2 at 2 p.m. He is a co-founder of the Hutch's Program in Immunology. Findings from his lab led to the first human trial of CD19 CAR-T cells of a defined T cell subset composition. With Fred Hutch collaborators, Riddell's recent CAR T-cell studies published in Science Translational Medicine and the Journal of Clinical Investigation have shown promise in patients with non-Hodgkin lymphoma and B-cell acute lymphocytic leukemia (ALL). Here's a video on Dr. Riddell's research: https:/
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- Dr. Aude Chapuis, a scientist in Fred Hutch's Clinical Research Division, will be giving a presentation, "Targeting pathogen-induced malignancies: Lessons learned from adoptive T cell transfer for merkel cell carcinoma," on April 1 at 3:45 p.m. Her research looks for ways to fine-tune adoptive T cell therapy through modifying T-cell receptors to target cancer-specific molecules. She presented findings in November showing the potential of genetically engineered T cells to target the molecule WT1 to prevent leukemia relapse. Her most recent paper, published in Science Immunology in February, demonstrated how to identify T cells best-suited to eliminating a patient's cancer. For an introduction to adoptive T cell therapy and her research, view this video: http://www.
fredhutch. org/ en/ news/ media-relations/ bios-photos/ chapuis-aude/ photos-graphics-video. html
At Fred Hutchinson Cancer Research Center, home to three Nobel laureates, interdisciplinary teams of world-renowned scientists seek new and innovative ways to prevent, diagnose and treat cancer, HIV/AIDS and other life-threatening diseases. Fred Hutch's pioneering work in bone marrow transplantation led to the development of immunotherapy, which harnesses the power of the immune system to treat cancer. An independent, nonprofit research institute based in Seattle, Fred Hutch houses the nation's first cancer prevention research program, as well as the clinical coordinating center of the Women's Health Initiative and the international headquarters of the HIV Vaccine Trials Network. Private contributions are essential for enabling Fred Hutch scientists to explore novel research opportunities that lead to important medical breakthroughs. For more information visit fredhutch.org or follow Fred Hutch on Facebook, Twitter or YouTube.