写的:
供Sapra以及
Senior Vice President, Biologics Engineering & 肿瘤学 Targeted Delivery, AstraZeneca
在澳门在线赌城娱乐, 澳门第一赌城在线娱乐的目标是重新定义当前癌症治疗的支柱——化疗和放疗方案——通过澳门第一赌城在线娱乐的发现平台，将高度靶向的抗体药物偶联物(adc)和放射性偶联物直接输送到癌细胞中.
Developing targeted cancer treatments
For decades, radiotherapy and chemotherapy have been the mainstays of cancer treatment. 虽然这些方法可能有效，但它们也会影响健康组织，导致脱靶效应.
澳门第一赌城在线娱乐迫切需要开发更有针对性的癌症治疗方法，就像导弹一样, delivering a powerful payload directly into cancer cells. Utilising our robust in-house capabilities and proprietary discovery platforms, we are developing advanced therapies to meet this need.
One promising approach we are working on is antibody-drug conjugates (adc). 这些分子由抗体组成，通过化学连接体连接到化疗有效载荷上. 当管理, 分子的抗体部分在肿瘤细胞表面表达特定的肿瘤相关或过度表达的蛋白质. The ADC is then taken into the cancer cell, where appropriate cleavage mechanisms release the cytotoxic payload. 这个过程比传统的化疗更有针对性地杀死癌细胞, sparing healthy cells.
在这, we are also developing radioconjugates, where targeting vehicles such as antibodies or their fragments, and small molecules or peptides are linked with radiotherapy agents. This approach delivers the radiation therapy to tumour cells, 使癌细胞能够以比传统的外部光束辐射更有针对性的方式被摧毁, offering more tailored treatments for patients.
自2000年美国食品和药物管理局(FDA)首次批准adc和2018年批准放射性缀合物以来, the development of these modalities has progressed rapidly. Our vision is to see them redefine cancer therapy regimens into the future.
Improving target specificity for ADCs and radioconjugates
For ADCs and radioconjugates to be able to redefine the cancer treatment space, 还有很多工作要做，比如让它们更好地瞄准癌细胞，减少脱靶效应, and thus enhancing tumour specificity.
为了实现这一目标，澳门第一赌城在线娱乐的重点是不断改进设计和工程过程. 这包括澳门第一赌城在线娱乐如何使用最先进的多组学方法识别新的靶标, 并且使用筛选方法，在药物发现过程的早期优先识别具有功能效应的候选药物. 通过将多种抗体生成方法与先进的自动化技术相结合, 澳门第一赌城在线娱乐现在能够以前所未有的速度和规模识别新的抗体疗法.
澳门第一赌城在线娱乐还使用复杂的蛋白质工程，通过将两种不同的抗体结合到一个分子中来增强肿瘤特异性, known as bispecific antibodies. 双特异性抗体可以同时与同一细胞上的两种不同的肿瘤相关抗原结合. By harnessing this unique property, adc和放射性缀合物可以比传统的对应物对癌细胞更具选择性. 这是因为双特异性adc或放射性偶联物可以潜在地将有效载荷传递给表达两种靶抗原的肿瘤细胞, 使正常的外周细胞和组织(通常只表达两种抗原中的一种)不受伤害.
澳门第一赌城在线娱乐也在设计更好的连接物，使澳门第一赌城在线娱乐的adc和放射性偶联物更有针对性. 不稳定的连接物可导致adc在影响健康组织的地方过早地减少其有效载荷. 使它们更加稳定，可以确保它们携带有效载荷进入肿瘤细胞. Another focus is to ensure that linkers can only be cleaved in tumour cells, so the payload is only activated in cancer cells, and that they remain inactive if the drug is taken up by healthy tissue.
Building a toolbox of payloads to match disease biology
No matter how precise an ADC or radioconjugate is, it can’t treat cancer without an effective payload, and not all payloads affect all tumours equally. 因此, 澳门第一赌城在线娱乐正致力于将ADC和放射共轭有效载荷与癌细胞的生物学特性相匹配, with the aim of making the cancer treatments more efficient.
将有效载荷与癌症相匹配的一个共同挑战是，肿瘤可能非常复杂和多样. Therapies that target just one biological mechanism can temporarily treat the cancer, but often resistance emerges, and the tumour recurs. To tackle this problem, we are exploring using multiple different payloads on one ADC. By using different mechanisms of action at the same time, 它有可能减少肿瘤的耐药性，并为患者提供更持久的益处.
We have also engineered ways to expand the targeted, ADC有效载荷通过所谓的旁观者效应在异质性肿瘤中的细胞毒性影响. 当有效载荷被设计用来杀死附近的靶阴性癌细胞时，就会发生这种情况，这些癌细胞最初不能被ADC治疗靶向.
A world of potential for ADCs and radioconjugates
澳门第一赌城在线娱乐的ADC和放射共轭平台只是澳门第一赌城在线娱乐重新定义癌症治疗的第一步. 澳门第一赌城在线娱乐对这些平台与其他治疗方式相结合的潜力感到兴奋.
例如, 澳门第一赌城在线娱乐正在探索将它们与不同作用机制的疗法结合起来，比如 cancer immunotherapies or molecules targeting the DNA damage response pathway, 或甚至是顺序给药的不同adc和/或放射性缀合物的组合.
Our transformational technologies such as proteomics, artificial intelligence and computational pathology are also helping us to accelerate the development of these novel treatment combinations. 在某些情况下, 它们让澳门第一赌城在线娱乐研究哪种抗体靶点最有可能对特定的癌症起作用，或者哪种患者最有可能受益.
澳门第一赌城在线娱乐的目标是继续利用这些技术，在未来澳门第一赌城在线娱乐可以同时处理开发的多个方面. As our ability to engineer our ADC and radioconjugate platforms evolve, so will our ability to develop precision medicines which target the right medicine, to the right patient, 在适当的时候.
We look forward to seeing how our programmes deliver over the coming years, and remain committed to continued innovation in this space.
