Comparative Oncology Program

比较肿瘤学项目

• 批准号: 9154403
• 负责人: Amy Leblanc
• 金额: $ 75.1万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9154403
• 关键词: Adjuvant Study; Animals; Antibodies; Antineoplastic Agents; Awareness; Behavior; Biological; Biological Assay; Biology; Biopsy; Brain Neoplasms; Cancer Biology; Cancer Model; Cancer Patient; Canis familiaris; Carcinoma; Cataloging; Catalogs; Clinic; Clinical; Clinical Research; Clinical Trials; Clinical Trials Network; Collaborations; Communities; Comparative Study; Conduct Clinical Trials; Contracts; Databases; Development; Devices; Diagnostic; Drug Industry; Educational workshop; Environmental Risk Factor; Evaluation; Exposure to; Extramural Activities; Failure; Felis catus; Formalin; Foundations; Freezing; Future; Gene Family; Generations; Genes; Genetic; Genomics; Goals; Gold; Government; Heterogeneity; Histology; Human; Imaging Device; In Vitro; Industry; Institute of Medicine (U.S.); Interview; Journals; Laboratories; Leadership; Link; Lymphoma; Malignant Bone Neoplasm; Malignant Neoplasms; Manuscripts; Mission; Modeling; Molecular Models; Motivation; Multi-Institutional Clinical Trial; Mus; NCI Center for Cancer Research; National Cancer Institute; Neoplasm Metastasis; Non-Hodgkin' s Lymphoma; Normal tissue morphology; Nose; Oligonucleotide Microarrays; Oral; Outcome; Patients; Pediatric Oncology Group; Pharmaceutical Preparations; Pharmacodynamics; Pharmacologic Substance; Pilot Projects; Population; Positioning Attribute; Pre-Clinical Model; Prevalence; Procedures; Process; Proteomics; Protocols documentation; Publishing; Reagent; Recurrence; Research; Research Infrastructure; Research Personnel; Resource Development; Resources; Role; Sampling; Schools; Scientist; Series; Serum; Services; Side; Sirolimus; System; Techniques; Testing; Therapeutic; Tissue Microarray; Tissues; Translating; Translational Research; Translations; Tumor Biology; Vendor; Veterinary Medicine; Work; anticancer research; base; cancer genomics; cancer therapy; chemotherapy; clinical application; comparative; conventional therapy; cost; design; dog genome; drug development; human disease; imaging agent; improved; in vivo; interest; mTOR Inhibitor; meetings; melanoma; molecular imaging; molecular modeling; multidisciplinary; neuro-oncology; non-invasive imaging; notch protein; novel; novel therapeutics; oncology; oncology program; oncolytic Vesicular Stomatitis Virus; osteosarcoma; pet animal; preclinical evaluation; preclinical study; programs; repository; response; scale up; standard care; therapeutic target; therapy resistant; tissue fixing; treatment strategy; tumor; virtual

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.

1. 开发必要的试剂盒，用于翻译和生物基础研究的比较模型的研究。COTC药效学核心：这是一个多学科的实验室，其“虚拟墙”由研究人员提供的服务组成，这些研究人员竞争机会为核心的分析/程序服务目录做出贡献。COTC PD Core旨在通过提供快速实施启动COTC研究所需的临床前研究的基础设施，促进与COTC试验发起人（制药公司）的早期讨论，然后无缝支持COTC试验的临床药效学和生物学终点。自成立以来，COTC PD核心已用于支持12项COTC试验中的6项。COTC PD核心完成了第三次RFP。犬寡核苷酸芯片：第一代和最近的第二代犬寡核苷酸芯片的优化技术和正常组织表达标准已经完成并启动。该微阵列目前可通过Affymetrix获得。2011-12财年：1)与Dr. Javed Khan的肿瘤基因组学部门合作完成了10个正常犬组织的基因特征鉴定手稿，并建立了一个可供公众检索的数据库。科学通报，2011;6(5):e17107。Epub 2011 5月31日。血清蛋白质组学（SELDI-TOFF）：与Timothy Veenstra（生物蛋白质组学计划）合作，优化了犬血清蛋白质组学分析的条件。验证抗体数据库：比较肿瘤学项目正在与商业抗体供应商和David Goldsmith博士合作开发用于犬类组织的验证抗体数据库，并向公众开放（http://ccr.cancer.gov/resources/cop/scientists/resource_antibody.asp）（癌症研究中心）。犬类比较肿瘤学基因组学联盟（CCOGC）：利用其中立立场，比较肿瘤学项目汇集了广泛的各方代表（学术界，工业界，政府），专注于犬类癌症的遗传学和生物学。CCOGC的共同利益将导致进一步的基因组学试剂/资源开发和合作努力，将犬癌症定性为人类疾病的分子模型。2007年，CCOGC启动了辉瑞犬比较肿瘤学和基因组学联盟生物标本库。犬类癌症生物标本库：通过与Fisher Bioservices签订的合同，建立了一个保存1800只癌症犬的冷冻和福尔马林固定组织的生物标本库。2013年，CCOGC开始根据科学价值发放组织。到目前为止，已经发布了1000多个样品。犬癌组织阵列：与Stephen Hewitt博士（CCR -组织阵列项目）合作，已经开发了许多强大的犬癌组织阵列。这些阵列包括结果相关犬淋巴瘤、结果相关犬骨肉瘤、结果相关鼻癌和多肿瘤犬组织阵列。多肿瘤犬组织阵列的2.0版本正在开发中。这些阵列试剂已经并将用于识别犬癌症的治疗靶点，以及癌症和转移生物学的研究，并用于协助未来COTC工作的临床前研究。2. 与校外比较肿瘤学项目建立多中心合作网络。在这个网络设计中，实施和管理涉及宠物动物的临床前试验，以评估新的癌症治疗策略；比较肿瘤学试验联盟：比较肿瘤学项目利用其中立的领导地位，汇集了20所一流的兽医学院，作为一个多中心临床试验网络进行合作。该网络通过比较肿瘤学项目的领导，为制药行业、国家癌症研究所的其他部门以及更广泛的学术界提供机会，通过使用狗身上自然发生的癌症作为药物开发的模型，为他们的癌症药物开发路径提供信息。迄今为止，比较肿瘤学试验联盟已经完成了12项临床试验，目前有2项开放试验。2015年特别值得关注的是：与EMD-Serono合作进行的COTC010是我们第一个由制药公司赞助的试验，评估了一种新型免疫细胞因子在犬黑色素瘤中的作用。这项研究发表在2015年第二季度的PlosOne上。COTC018：与赛诺菲-安万特合作的iniparib对癌症犬的评估于2013年完成，目前正在出版中。COTC007b：与NCI-DCTD （Doroshow/Pommier）合作的3种吲哚异喹啉类药物的临床前评估正在进行中，预计将于2015年第四季度完成。2014年Q3， COTC020研究：评估口服mTOR抑制剂雷帕霉素对骨肉瘤犬的治疗作用。COTC020研究是一项大型骨肉瘤犬辅助研究的先导研究，评估口服雷帕霉素。这项辅助研究将成为5-5-5运动的一部分，由莫里斯动物基金会和儿童肿瘤组织支持，将在患有骨原性肉瘤的宠物狗身上进行临床试验，以评估治疗犬和人类骨癌的新疗法。他们的目标是在五年内进行五次临床试验，总共投入500万美元。5-5-5的监督将由科学顾问委员会负责。Amy LeBlanc博士，新任命的比较肿瘤学项目主任，任职于SAB。COP的实验室组成部分将通过一系列已建立的体外/离体/体内转移生物学试验（SRB，划痕试验，PuMA，实验和自发转移）来评估这些药物，从而协助对该活动的药物进行审查。最后，COTC024是第一个评估生物制剂的COTC试验，一种溶瘤性VSV构建物，用于荷瘤犬。这项由制药公司赞助的研究与梅奥诊所合作，预计将于2016年第一季度开始。3. 提高癌症研究界对适当使用自然发生的癌症模型的认识。Drs。Khanna和LeBlanc经常受邀演讲，向学术界和工业界团体介绍药物开发比较方法的特点。一项新的脑肿瘤倡议目前正在进行中。计划于2015年9月召开一次会议，汇集人类和兽医脑肿瘤领域的领导人。2015年6月8日至9日，在美国医学研究所（IOM）举行了一场名为“患有自然肿瘤的宠物临床研究在转化性癌症研究中的作用”的研讨会。自这次研讨会以来，LeBlanc博士已经回应了来自科学/贸易和非专业新闻期刊的许多关于比较肿瘤学项目的采访请求。4. 加强和建立内部NCI的新合作。与神经肿瘤科（Mark Gilbert博士）和分子成像项目（Peter Choyke博士）的具体合作项目正在进行中，并与上述校外努力有关。一个新的联盟，利用现有COTC的成员和专业知识，将侧重于犬脑肿瘤的比较价值；计划于2015年9月14日至15日召开计划会议，启动这项工作。LeBlanc博士还获得了一项新的动物研究协议的批准，允许携带肿瘤的宠物狗进入分子成像诊所参与新的显像剂研究，该研究计划于2015年第四季度开始。

项目成果

Defining the Pharmacodynamic Profile and Therapeutic Index of NHS-IL12 Immunocytokine in Dogs with Malignant Melanoma.

• DOI: 10.1371/journal.pone.0129954
• 发表时间: 2015
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Paoloni M;Mazcko C;Selting K;Lana S;Barber L;Phillips J;Skorupski K;Vail D;Wilson H;Biller B;Avery A;Kiupel M;LeBlanc A;Bernhardt A;Brunkhorst B;Tighe R;Khanna C
• 通讯作者: Khanna C