Developmental Research Program

Seattle Cancer Consortium Breast SPORE

Developmental Research Program

Director: Peggy L. Porter, MD

Since the SPORE was funded in September 2010, six requests for applications have been announced, resulting in 63 applications and over $1.1 million distributed for support of 26 developmental projects.  

Dr. Matthias Stephan

An implant designed by Dr. Matthias Stephan that concentrates immune cells directly at tumor sites where they can unite to clear away the adjacent tumor.

Photo by Matthias Stephan / Fred Hutch

Applications came from all divisions within the Fred Hutch and the UW departments of nursing, immunology, medical genetics, medical oncology, medicine, imaging, pathology, surgery, biochemistry, epidemiology, radiation oncology, medicinal chemistry, pharmacology, nuclear medicine, biophysiology, psychiatry, bioengineering and physiology. Three of the funded pilots have contributed data to full project development; five have resulted in publications and/or grant applications.

The developmental projects supported include a broad selection of research on breast cancer etiology, mechanical relapse prevention strategies, metabolic diversity, immunotherapy, radiopharmaceuticals for imaging, gut microbiome, biomarkers of treatment, detection and resistance, and the effect of breast cancer on patient financial status.  The developmental research program (DRP) has been very active and productive supporting early studies that have gone on to obtain additional funding.

Studies funded by DRP

  • The project completed by Dr. Matthias Stephan to develop an implantable device for the prevention of metastatic tumor relapse after breast-conserving surgery has made substantial progress performing preclinical testing of this system. They found that the implants efficiently disperse and support breast tumor-targeting T cells throughout tumor resection beds and their associated lymph nodes, and provide protection against tumor relapse, whereas analogous transfusions of tumor-reactive lymphocytes fail to prevent relapse. The results demonstrate that launching cancer-fighting T cells from polymeric devices can comprise a safe and effective therapy, and may propel the entry of this approach into the standard of care for breast cancer patients. Their key findings are published in Nature Biotechnology60, a manuscript that was also highlighted in Nature Biotechnology61, Science Translational Medicine62 and BioCentury63. Dr. Matthias has also obtained grant funding based on pilot results: RO1CA181413-01 (NIH-NCI), “Preventing tumor relapse with biomaterial-supported lymphocyte implants”.
  • Drs. V.K Gadi and Christopher Kemp capitalized on their DRP project New Targets For Doxorubicin Resistant Breast Cancer to obtain critical preliminary data that led to U01 award from the NCI (UO1 CA176303-01; Chris Kemp, PI, V.K. Gadi, Co-investigator) that will develop an integrated computational and functional genomics discovery engine for preclinically validated cancer drug targets. They have also submitted a R01 (RO1 CA195792; Christopher J. Kemp, PI, V.K. Gadi, Co-Investigator) to establish a preclinical translational program to validate novel targeted therapies for triple negative breast cancer. Advances made through the U01 and other funding will be brought back to the SPORE for discussion of additional translational objectives and clinical trial opportunities.
  • Dr. Andre Lieber, UW, has received more than one DRP and he has made substantial progress in the translation of his small recombinant protein (JO) to the clinic. JO allows for better tumor penetration of therapeutic monoclonal antibodies and chemotherapy drugs and in the context of the pilot award, Dr. Lieber has demonstrated in xenograft models of triple negative breast cancer that JO greatly increased the therapeutic efficacy of Abraxane and Erbitux64. He also showed in a study in non-human primates that JO injection was well tolerated65. The data produced with the support from the Breast Cancer SPORE pilot grant helped to attract additional funding from the NIH (R21CA193077; SBIR R43 CA183379-01, Phase I and an industry partner. He is also evaluating JO in ovarian cancer and has a project in the FHCRC Ovarian SPORE. We considered his project as a full project in the renewal and decided that he was well positioned to move a clinical trial forward without direct SPORE funding. Dr. Lieber will continue to interact and collaborate with SPORE clinicians to design and implement a phase I trial of JO and Taxol.
  • An exciting collaboration between the SPORE and Dr. Scott Ramsey’s Hutchinson Institute for Outcomes Research (HICOR) program, created to reduce the human and economic burden of cancer for patients, families and society, was developed with DRP funding into a project led by Drs. Veena Shankaran and Ramsey. The research areas of comparative effectiveness analysis and health economics are not generally considered appropriate for the SPORE mechanism. However, the strategy to develop an intervention with a financial navigation tool for patients with breast cancer has potential to impact the lives of women with breast cancer and improve care. We will continue to work with the group to explore possible translational aspects of the HICOR research.

DRP funding supports new collaboration between Dr. Mary-Claire King and Dr. Garnet Anderson of the Women’s Health Initiative (WHI) for genetic testing of women in the WHI for inherited mutations in breast cancer. The SPORE Executive Committee and advisory boards selected this as a project in the 2015 renewal application.