Development of a Multi-Panel Multiplex Immunofluorescence Breast Cancer Immunophenotyping Assay

多组多重免疫荧光乳腺癌免疫表型分析的开发

• 批准号: 9151812
• 负责人: David Schwartz
• 金额: $ 50.75万
• 依托单位: CELL IDX, INC.
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-25 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9151812
• 关键词: Affinity; Antibodies; Antigens; Archives; Biological Assay; Biopsy; Breast biopsy; Cancer Diagnostics; Cells; Clinic; Clinical; Clinical Research; Collaborations; Contractor; Cytokeratin-14 Staining Method; Detection; Development; Diagnosis; Diagnostic; Disease; Enzymes; Epidermal Growth Factor Receptor; Estrogen Antagonists; Estrogen Receptors; Flow Cytometry; Fluorescence; Future; Generations; Goals; Haptens; Health; Immobilization; Immunofluorescence Immunologic; Immunohistochemistry; Immunophenotyping; Label; Link; Malignant Neoplasms; Mammary Gland Parenchyma; Mammary Neoplasms; Methods; Morphology; Oncologist; Oryctolagus cuniculus; Pathologist; Peptide antibodies; Peptides; Phase; Phenotype; Preparation; Process; Progesterone Receptors; Protocols documentation; Reagent; Reproducibility; Research; Series; Signal Transduction; Slide; Specimen; Staining method; Stains; System; Technology; Testing; Therapeutic; Tissue Microarray; Tissues; Translations; Tumor Markers; Tumor Tissue; Validation; Vimentin; base; biomarker panel; cancer subtypes; cancer type; clinical Diagnosis; clinical research site; commercialization; diagnostic assay; malignant breast neoplasm; novel; peptide analog; programs; research study; tool; treatment planning; triple-negative invasive breast carcinoma; tumor

 DESCRIPTION (provided by applicant) The overall aim of the proposed research and commercialization plan is to develop a technology that will yield a quantitative, multiplex IHC immunophenotyping assays for breast cancer clinical diagnosis and research. These assays will allow the oncologist to accrue the maximum amount of information on which to base diagnosis and treatment plans using a minimum amount of tissue, allow greater reproducibility of testing between clinical sites and provide quantifiable information within the context of tissue morphology. Validation of this platform technology with the breast cancer assays will allow us to expand use of the technology to other multiplex marker panels, allowing the possibility of a series of tests providing branched diagnosis resulting in better treatment decisions. This platform technology can then be expanded to other cancers and diseases encompassing both clinical diagnostics as well as research reagents. Expanding on our initial "proof-of-principle" studies, we will demonstrate multiplex fluorescent staining using our UltraPlex-BC1 panel (ER - estrogen receptor, PR - progesterone receptor, HER2 and Ki-67) on invasive breast cancer biopsies using our existing detection antibodies/technology whilst at the simultaneously develop second-generation detection reagents to expand our future plexing capacity. The UltraPlex-BC1 panel provides subtyping of breast biopsies into 4 major subtypes, one of which is a particularly aggressive form lacking the main ER/PR/HER2 markers, called triple negative breast cancer. Our second panel, Ultraplex-BC2 aims to subdivide the triple negative tumors into the more aggressive basal and less aggressive non-basal forms. Using our second-generation detection reagents we will demonstrate sensitive multiplex IHC staining of invasive breast tumors and compare this to current technology that employs single staining/enzyme labeled detection reagents. Finally we will validate both assays using a series of typed breast tumor tissues.

 描述（由申请人提供）拟议研究和商业化计划的总体目标是开发一种技术，该技术将产生用于乳腺癌临床诊断和研究的定量、多重IHC免疫表型分析。这些测定将允许肿瘤学家使用最少量的组织积累最大量的信息，以作为诊断和治疗计划的基础，允许临床研究中心之间的测试具有更大的再现性，并在组织形态学的背景下提供可量化的信息。该平台技术与乳腺癌检测的验证将使我们能够将该技术的使用扩展到其他多重标记物组，从而允许一系列测试提供分支诊断的可能性，从而导致更好的治疗决策。该平台技术可以扩展到其他癌症和疾病，包括临床诊断和研究试剂。 在我们最初的“原理验证”研究的基础上，我们将使用我们现有的检测抗体/技术，使用我们的UltraPlex-BC 1面板（ER -雌激素受体，PR -孕激素受体，HER 2和Ki-67）对浸润性乳腺癌活检进行多重荧光染色，同时开发第二代检测试剂，以扩大我们未来的复合能力。UltraPlex-BC 1面板将乳腺活检分为4种主要亚型，其中一种是缺乏主要ER/PR/HER 2标志物的特别侵袭性形式，称为三阴性乳腺癌。我们的第二组，Ultraplex-BC 2旨在将三阴性肿瘤细分为更具侵袭性的基底和侵袭性较低的非基底形式。使用我们的第二代检测试剂，我们将证明侵袭性乳腺肿瘤的敏感性多重IHC染色，并将其与采用单一染色/酶标记检测试剂的当前技术进行比较。最后，我们将使用一系列分型的乳腺肿瘤组织来验证这两种检测方法。