實驗室自動化與篩選協會2013亞洲會展短期培訓課程簡介

短期培訓課程I ：生物制劑研發中的高通量篩選

Junma Zhou，博士，上海藥明康德新藥開發有限公司

劉潔穎博士，上海藥明康德新藥開發有限公司

　　In Scope of Short Course

　　- Overview of high-throughput techniques in terms of therapeutic antibody lead finding

　　- Details of antibody screening assay design and case studies, along with discussions of the relative strengths of different assay formats in therapeutic antibody discovery

　　Focus

　　- Methods in high-throughput screening that characterize the binding and mode of action for antibodies to target proteins

　　- High-throughut binding screen using FACS and homogeneous assays that overcome problems with automating ELISA

　　- Binding affinity screen and epitope binning in lead finding using high-throughput, label-free assays

　　The therapeutic market for monoclonal antibodies has grown fast. The rapid screening of hybridoma and phage supernatants for antibodies is central to efficient antibody generation. Here we introduce the homogeneous assay using a newly developed equipment Mirrorball which is a laser-scanning fluorescence microplate cytometer. Compared to the traditional screen method using ELISA, this system is more robust, requires smaller sample size and is able to reliably detect antibodies targeting low-abundance cell-surface proteins. We will discuss how to use this technique for antibody screening in both cell-based and bead-based assays.

　　During the process of therapeutic antibody discovery, in most cases supernatants from hybridoma and phage are not suitable for functional assays. Therefore when facing thousands of hits against target proteins subsequent to primary binding screen, effective methods are needed to further narrow down the number of drug candidates using biochemical assays. In this short course we will discuss how the SPR-based label-free assays enables screening of antibody binding characteristics; how to use these assays to characterize the epitope binding regions for antibody panels, facilitate their organization into epitope groups or bins and how antibody on/off rates data are used to guide clone selection and antibody engineering studies.

短期培訓課程II ： 腫瘤藥物發現中的細胞分析測驗方法的開發

沈余紅博士

上海藥明康德新藥開發有限公司，腫瘤學部，高級主任

　　Recent advancesof targeted therapies havegreatly shifted the drug discovery paradigm. With the much better understanding of the molecular and cellular mechanisms of tumor formation and cancer as a disease, reliable cell based assays which truthfully reflect the mechanism of the targets and assess phenotypes most directly associated with the target mechanism have become a critical component of oncology drug discovery for both new chemical entities and biologics. Especially in small molecule drug discovery, once the targets are validated, new chemical entities are screened in a variety of activity assays to determine the effectiveness of the chemical entities. These assays are often organized with the flow of the primary biochemical assays to measure activity against the target of interest, followed by the cell based assays to determine the effectiveness of the compounds to the specific targets or to the cell functions. These cell-based assays are highly demanded and valuable to predict in vivo efficacy of the compounds and guide in vivo studies.

　　Compared with biochemical assays, cell based assays involve many more variables. Thus many parameters such as assay formats and conditions including cell line selection, cell growth conditions, other pathway interference etc. need to be carefully evaluated and controlled to establish reliable assays. In this short course, we will address the challenges and guiding principles of setting up reliable and robust cell based assays through some case study examples. We will focus on discussing some of the highly used mechanism based cell based assays such as ELISA, In-Cell Western or AlphaScreen, as well as some of the widely used oncology cell based phenotypic assays such as viability and proliferation, apoptosis assays, colony formation assays, migration and angiogenesis assays etc.

短期培訓課程III ： 受體利用率：一個研究體外活性與體內效能相關性的方法

樂思遠博士

上海藥明康德新藥開發有限公司

　　G蛋白偶聯受體家族已然成為今后制藥業藥物靶點研究的重中之重，研究配體-受體相互作用機理以及受體激活和失活產生的功能性結果對于眾多功能性紊亂疾病的藥物研發有著重要意義。

　　這堂課我們會簡要的介紹機體組織水平的受體結合研究，包括在體外利用嚙齒動物腦組織提取細胞膜進行的G蛋白偶聯受體結合試驗。與體內受體的表達水平相比，重組受體表達系統的表達量往往會高上成千上萬倍。我們將以昆蟲病毒BacMam系統為例，為大家講解它獨特的受體表達調控機理以及基于該系統開發的各種檢測平臺。

　　配體與受體的研究，關鍵是要找到藥物在體內與目標靶點作用時能夠產生持續藥效的濃度，這正好可以通過對受體利用率的研究來實現，該方法對于研究體外活性與體內效能的相關性至關重要，它能為前臨床研究提供有效的劑量依據。我們會對在前臨床與臨床階段利用多種途徑(離體，體內，勻漿或放射自顯影技術)對受體利用率進行定量檢測的這種方法及其作用進行討論，并用幾個實例來說明該方法在轉譯神經科學領域的重要地位。