Comparative Oncology Program

Leblanc, Amy

Abstract

1. Develop essential reagent kit for the study of comparative models in translational and biology-based research. Specific reagents/resources include: COTC Pharmacodynamic Core: This multidisciplinary effort operates as a laboratory with virtual walls consisting of services provided by investigators who have competed for the opportunity to contribute to the assay/procedure service catalog of the Core. The COTC PD Core is meant to facilitate early discussions with COTC trial sponsors (pharmaceutical companies) by providing the infrastructure for rapid implementation of preclinical studies needed to initiate a COTC study and then seamlessly support the clinical pharmacodynamic and biological endpoints of COTC trials. Since its inception the COTC PD Core has been used to support 6 of 12 COTC trials. The COTC PD Core completed its 3rd RFP. Canine oligonucleotide microarray: Optimized techniques and normal tissue expression standards for both a first generation and more recently a second generation canine oligonucleotide microarray have been completed and initiated. This microarray is currently available through Affymetrix. In FY 2011-12: 1) Manuscript to characterize the gene signatures of 10 normal canine tissues in collaboration with Dr. Javed Khan's Oncogenomics Section, and establish a database available for public search was completed. PLoS One. 2011;6(5):e17107. Epub 2011 May 31. Serum proteomics (SELDI-TOFF): Conditions for canine serum proteomic analysis have been optimized in collaboration with Timothy Veenstra (Biological Proteomics Program). Validated antibody data base: A database of validated antibodies for use in canine tissues is being developed within the Comparative Oncology Program in collaboration with commercial antibody vendors and Dr. David Goldsmith and is available to the public (http://ccr.cancer.gov/resources/cop/scientists/resource_antibody.asp) (Center for Cancer Research). Canine Comparative Oncology Genomics Consortium (CCOGC): Using its neutral position, the Comparative Oncology Program has brought together a broad representation of parties (academic, industry, government) focused on the genetics and biology of cancer in dogs. The shared interests of the CCOGC will result in further genomics reagent/resource development and collaborative efforts that will characterize canine cancers as molecular models of human disease. In 2007, the CCOGC launched the Pfizer-Canine Comparative Oncology and Genomics Consortium Biospecimen Repository. Canine Cancer Biospecimen Repository: A biospecimen repository of frozen, and formalin fixed tissues from 1800 dogs with cancer has been established through a contract with Fisher Bioservices. In 2013 the CCOGC began releasing tissues based on scientific merit. To date over 1000 samples have been released. Canine Cancer Tissue Arrays: In collaboration with Dr. Stephen Hewitt (CCR - Tissue Array Project), a number of robust canine cancer tissue arrays have been developed. These arrays include outcome linked canine lymphoma, outcome linked canine osteosarcoma, outcome linked nasal carcinoma, and a multi-tumor canine tissue array. Version 2.0 of the multi-tumor canine tissue array is under development. These array reagents have and will be useful for the identification of therapeutic targets in canine cancers, and the study of cancer and metastasis biology/and are used to assist with pre-clinical studies for future COTC efforts. 2. Develop multi-center collaborative network with extramural comparative oncology programs. Within this network design, implement and manage pre-clinical trials involving pet animals that will evaluate novel therapeutic strategies for cancer; Comparative Oncology Trial Consortium: The Comparative Oncology Program has used its neutral leadership position to bring together twenty top-notch schools of veterinary medicine to collaborate as a multi-center clinical trial network. This network works together through the leadership of the Comparative Oncology Program to offer the pharmaceutical industry, other parts of the National Cancer Institute, and the broader academic community the opportunity to inform their cancer drug development paths by using naturally occurring cancers in dogs as models for drug development. The Comparative Oncology Trials Consortium has completed twelve clinical trials thus far and currently has two open trials. Of particular interest for 2015: COTC010, performed in collaboration with EMD-Serono, was our first pharma-sponsored trial evaluating a novel immunocytokine in canine melanoma. This study was published in PlosOne in Q2 2015. COTC018: The evaluation of iniparib in dogs with cancer in collaboration with Sanofi-Aventis was completed in 2013 and is currently in press. COTC007b: The preclinical evaluation of 3 indenoisoquinolines, in collaboration with NCI-DCTD (Doroshow/Pommier), is ongoing and expected to be completed in Q4 2015. In Q3 2014, study COTC020: Evaluation of orally administered mTOR inhibitor Rapamycin in dogs with osteosarcoma opened for accrual. Study COTC020 is pilot study for a larger adjuvant study in dogs with osteosarcoma evaluating oral rapamycin. This adjuvant study will be part of the 5-5-5 campaign, supported by Morris Animal Foundation and the Children's Oncology Group, will conduct clinical trials in pet dogs with osteosarcoma to assess novel therapies that show promise for the treatment of canine and human bone cancers. The goal is five clinical trials, in five years at a total of $5 million. Oversight of the 5-5-5 will come from a Scientific Advisory Board. Dr. Amy LeBlanc, newly appointed Director of the Comparative Oncology Program, serves on the SAB. The laboratory component of the COP will assist in the vetting of agents slated for this campaign by assessing them in a series of established in vitro/ex vivo/in vivo assays of metastasis biology (SRB, scratch assay, PuMA, experimental and spontaneous metastasis). Finally, COTC024 is the first COTC trial to evaluate a biologic agent, an oncolytic VSV construct, in tumor-bearing dogs. This pharma-sponsored study in collaboration with the Mayo Clinic, is slated to begin in Q1 of 2016. 3. Increase the awareness of the appropriate use of naturally occurring cancer models within the cancer research community. Both Drs. Khanna and LeBlanc are frequently invited speakers asked to present the attributes of the comparative approach to drug development to both academic and industry groups. A new brain tumor initiative is currently underway. A meeting is being planned in September of 2015 to bring together leaders in the field of brain tumors from both the human and veterinary side. A workshop titled The Role of Clinical Studies for Pets with Naturally Occurring Tumors in Translational Cancer Research was held on June 8-9, 2015 at the Institute of Medicine (IOM). Since this workshop, Dr. LeBlanc has responded to numerous requests for interviews regarding the Comparative Oncology Program from scientific/trade and lay press journals. 4. Strengthen and establish new collaborations within intramural NCI. Specific collaborative projects with the Neurooncology Branch (Dr. Mark Gilbert) and the Molecular Imaging Program (Dr. Peter Choyke) are underway and have ties to the extramural efforts described above. A new consortium, drawing upon membership and expertise within the existing COTC, will focus on the comparative value of canine brain tumors; a planning meeting to launch this effort is planned for Sept 14-15, 2015. Dr. LeBlanc has also received approval of a new Animal Study Protocol to allow tumor-bearing pet dogs to access the Molecular Imaging Clinic for participation in novel imaging agent studies, which are slated to begin in Q4 2015.