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2006 Scientific Report

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Van Andel Research

Van Andel Research Institute | Scientific Report A second established project continues work initiated by Rick Hay and colleagues while he was a member of the Laboratory of Molecular Oncology. Since 2001 we have been evaluating a group of antibodies (designated MetSeek) that recognize the Met receptor tyrosine kinase. Met plays a key role in causing cancers to become more aggressive, so that they spread to nearby tissues (invasion) and/or travel through the bloodstream or lymph channels to distant organs (metastasis). We previously showed that two MetSeek agents used as originally produced in the laboratory (by hybridoma cells) are useful for nuclear imaging of Met-expressing human tumors (xenografts) grown under the skin of immunodeficient mice. In the past year, in collaboration with our colleagues at VARI and with our outside collaborators in Ann Arbor, Detroit, and East Lansing, we have shown further that smaller versions of MetSeek such as Fab fragments also generate satisfactory nuclear images of Met-expressing xenografts. We are currently characterizing other smaller versions of MetSeek as potential nuclear imaging agents and as carriers of anticancer molecules; exploring new ways of complexing radioactive atoms with MetSeek agents for improved ease of use and future clinical application; and systematically evaluating the use of MetSeek in tumors having the highest prevalence of abnormal Met expression. External Collaborators 36 Our laboratory depends critically on intramural and extramural collaborations to address our research themes. Our extramural collaborators encompass scientists and physicians at the Department of Veterans Affairs Healthcare System in Ann Arbor; the University of Michigan in Ann Arbor; Michigan State University in East Lansing; ApoLife, Inc., in Detroit; Henry Ford Hospital in Detroit; West Michigan Heart, P.C., in Grand Rapids; St. Mary’s Mercy Medical Center in Grand Rapids; Fred Hutchinson Cancer Research Center in Seattle; the Gerald P. Murphy Foundation in West Lafayette, Indiana; the National Cancer Institute in Bethesda, Maryland; and the University of Illinois in Champaign-Urbana. Recent Publications Hay, Rick V., Brian Cao, R. Scot Skinner, Yanli Su, Ping Zhao, Margaret F. Gustafson, Chao-Nan Qian, Bin T. Teh, Beatrice S. Knudsen, James H. Resau, Shuren Shen, David J. Waters, Milton D. Gross, and George F. Vande Woude. 2005. Nuclear imaging of Met-expressing human and canine cancer xenografts with radiolabeled monoclonal antibodies (MetSeek). Clinical Cancer Research 11(19): 7064s–7069s. Jiao, Yongjun, Ping Zhao, Jin Zhu, Tessa Grabinski, Zhengqing Feng, Xiaohong Guan, R. Scot Skinner, Milton D. Gross, Rick V. Hay, Hiroshi Tachibana, and Brian Cao. 2005. Construction of human naïve Fab library and characterization of anti-Met Fab fragment generated from the library. Molecular Biotechnology 31(1): 41–54.

VARI | 2006 Office of Translational Programs In July 2005 the Office of Translational Programs (OTP) became the administrative home base for activities overseen by the Deputy Director for Clinical Programs (DDCP). The role of OTP is to promote and facilitate collaborative programs involving the Van Andel Research Institute and other institutions in the realm of translational medicine. OTP has accomplished the following during our inaugural year of formal operation. • Serving as the interim administrative home for the Grand Rapids-GMP project: With funding from the state of Michigan and the federal Health Resources and Services Administration, this project—a partnership venture between VARI and Grand Valley State University (GVSU)—will build and operate a Good Manufacturing Practices facility for preparing biological agents and small molecules to be used in early phase clinical trials, primarily serving academic and commercial investigators in Michigan and the Midwest. In December 2004, administrative oversight of the project was assigned to DDCP. First a planning group and then a GR-GMP Board of Directors (five representatives from VARI and GVSU) have directed project progress during the past year. A facility director has been recruited and brought on board, and a dedicated business entity is being incorporated to manage details of facility construction and operation. • Hosting regional meetings of the Michigan Cancer Consortium (MCC): As an active member of the MCC, VARI is committed to participating in statewide programs to reduce the burden of cancer in Michigan. In 2005, we and other MCC members gained approval to launch a series of meetings with the purpose of identifying fresh initiatives that better suited the needs of western Michigan and, by doing so, to reinvigorate member participation. Since December 2005 we have held monthly meetings of a focus group comprising MCC members within Kent County. We have identified specific regional deficiencies in delivery of cancer-related patient care, and we are preparing a formal funding proposal to support a pilot project on this front. 37 • Promoting new inter-institutional collaborations and providing resources for funding proposals: OTP has provided personnel, logistical support, grant preparation expertise, meeting venues, and seed funding for new inter-institutional collaborations seeking extramural funding through the first round of proposals submitted to the 21st Century Jobs Fund (Michigan Economic Development Corporation), as well as administrative assistance for generating funding requests to other agencies. The two largest programs we are promoting in this fashion are the Innovative Clinical Research Alliance (ICRA), spearheaded by Dr. Craig Webb and collaborators from regional healthcare and clinical trial entities; and a biotrust project initiated by Drs. Clark Radcliffe and Nigel Paneth of Michigan State University. At this writing, we are awaiting the results of peer review on these and our smaller applications. Staff Rick Hay, Ph.D., M.D., F.A.H.A. Troy Carrigan

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