ADC早研偶联实习生
岗位职责:
1. 偶联样品的制备与工艺优化
1. Conjugation Sample Preparation and Process Optimization
a) 独立完成ADC偶联样品的全流程制备,包括抗体预处理(如还原/修饰)、偶联反应条件优化(pH、温度、摩尔比)、纯化(超滤管过滤、切向流过滤、亲和/疏水层析)及制剂稳定性测试等。
a) Independently execute end-to-end preparation of ADC conjugation samples, including antibody pretreatment (e.g., reduction/modification), optimization of conjugation reaction conditions (pH, temperature, molar ratio), purification (ultrafiltration tube filtration, tangential flow filtration, affinity/hydrophobic chromatography), and formulation stability testing.
b) 建立标准化偶联操作流程(SOP),确保样品批间一致性,支持高通量筛选及下游功能验证。
b) Establish standardized conjugation operating procedures (SOPs) to ensure batch-to-batch consistency of samples, supporting high-throughput screening and downstream functional validation.
2. ADC候选分子设计与开发
2. ADC Candidate Molecule Design and Development
a) 熟悉抗体-药物偶联物(ADC)的早期研发,包括但不限于化学偶联(如半胱氨酸/赖氨酸偶联)新型偶联策略探索(如定点偶联、酶促偶联、非天然氨基酸插入等),优化药物抗体比(DAR)及连接子(Linker)设计。
a) Familiar with the early-stage research and development of antibody-drug conjugates (ADCs), including but not limited to chemical conjugation strategies (e.g., cysteine/lysine conjugation), novel conjugation approaches (e.g., site-specific conjugation, enzymatic conjugation, non-natural amino acid incorporation), and optimization of drug-to-antibody ratio (DAR) and linker design.
b) 开发高均一性、高稳定性的ADC候选分子,支持创新靶点的概念验证(POC)。
b) Develop highly homogeneous and stable ADC candidates to support proof-of-concept (POC) validation for innovative targets.
3. ADC表征与机制研究
3. ADC Characterization and Mechanism Studies
a) 利用HPLC(如HIC、SEC)、质谱(MS)、毛细管电泳(CE-SDS)等技术,完成ADC的理化性质分析(如DAR、游离毒素、聚集度)及结构确证。
a) Perform physicochemical characterization (e.g., DAR, free toxin analysis, aggregation assessment) and structural confirmation of ADCs using techniques such as HPLC (e.g., HIC, SEC), mass spectrometry (MS), and capillary electrophoresis (CE-SDS).
b) 结合体外功能实验(如靶点结合活性、细胞内吞、溶酶体释放效率)阐明ADC的作用机制。
b) Elucidate ADC mechanisms of action by integrating in vitro functional assays (e.g., target binding affinity, cellular internalization, lysosomal release efficiency).
4. 生物活性与药效评估
4. Biological Activity and Efficacy Evaluation
a) 设计并执行ADC的体外活性检测(如细胞毒性实验、增殖抑制、抗原依赖性内吞),优化体外-体内相关性,建立与执行ADC(含linker与payload)体外细胞活性与安全性评估方法,如靶标过表达细胞系建立、细胞杀伤分析、旁观效应、PBMC活性、ADCC/ADCP/CDC活性、稳定性评估等。
a) Setup ADC (including linker and payload) in vitro activity assays and safety evaluation assays, such as building target overexpression cell line, cellular cytotoxicity assay, bystander effect assay, PBMC activity assay, ADCC/ADCP/CDC activity assay, satbility assay.
5. 蛋白质工程与表达支持
5. Protein Engineering and Expression Support
a) 参与抗体/蛋白的工程化改造(如降低免疫原性、增强偶联位点可及性),优化表达体系(CHO/HEK293)以适配偶联需求。
a) Participate in antibody/protein engineering (e.g., immunogenicity reduction, conjugation site accessibility enhancement) and optimize expression systems (CHO/HEK293) for conjugation compatibility.
b) 熟悉蛋白质纯化基础技术(如亲和层析、离子交换),确保候选分子的稳定性及偶联兼容性。
b) Apply foundational protein purification techniques (e.g., affinity chromatography, ion exchange) to ensure candidate molecule stability and conjugation suitability.
6. 实验室管理
6. Laboratory management
a) 负责SMP/SOP 文件起草、发布、升版等工作。
a) Be responsible for the drafting, release, upgrading and other work of SMP/SOP documents.
b) 确保实验室5S管理的相关要求。
b) Ensure the relevant requirements of laboratory 5S management.
任职资格:
1. 全日制本科及以上学历,肿瘤学、细胞生物学、免疫学、生物化学等相关专业。
1. Full-time bachelor degree or above, major in oncology, cell biology, immunology, biochemistry, etc.
2. 熟悉分子类、化学类、细胞类实验相关操作,有ADC或抗体类工作相关经验更佳。例如:抗体开发、抗体工程、双抗经验、具有小分子毒素-连接子(Payload-Linker)设计经验或ADC药物代谢(PK/PD)研究背景等。
2. Familiar with molecular, chemical, and cell-based experimental operations. Experience in ADC or antibody-related work is preferred. For example, experience in antibody development, antibody engineering, bispecific antibodies, small molecule toxin-linker (Payload-Linker) design, or ADC drug metabolism (PK/PD) research, etc.
3. 具有良好的实验习惯、细致谨慎、责任心强。
3. Good experimental habits, meticulous and careful, strong sense of responsibility.
4. 具有良好的英文读写能力,熟悉各类文献的检索。
4. Good English reading and writing skills, familiar with the search of various literature.
5. 具有良好的沟通能力和执行能力。
5. Good communication skills and execution skills.
6. 具有良好的团队意识,富有合作精神。
6. Have a good sense of teamwork and full of cooperation spirit.