Written by:
Puja Sapra
生物制品工程高级副总裁 & 肿瘤靶向递送，澳门在线赌城娱乐
At AstraZeneca, we have the ambition to redefine the backbone of current cancer treatment – chemotherapy and radiotherapy regimens – with our discovery platform that delivers highly targeted 抗体药物配合 (ADCs) and radioconjugates directly into cancer cells.
开发靶向癌症治疗方法
几十年来，放疗和化疗一直是癌症治疗的主要手段. While these approaches can be effective, they also affect healthy tissue, causing off-target effects.
There is an urgent need to develop more targeted cancer treatments that act like a guided missile, 直接向癌细胞传递强大的有效载荷. 利用澳门第一赌城在线娱乐强大的内部能力和专有的发现平台, 澳门第一赌城在线娱乐正在开发先进的疗法来满足这一需求.
澳门第一赌城在线娱乐正在研究的一个很有前途的方法是 抗体药物配合 (ADCs). These molecules consist of an antibody attached via a chemical linker to a chemotherapy payload. When administered, the antibody part of the molecule homes in on tumour cells that express a specific tumour associated or overexpressed protein on their surface. 然后将ADC带入癌细胞, 合适的裂解机制在哪里释放细胞毒性载荷. This process kills the cancer cell in a more targeted way than traditional chemotherapy, 保护健康细胞.
Alongside this, 澳门第一赌城在线娱乐也在开发放射性缀合物, 靶向载体如抗体或其片段在哪里, 小分子或多肽与放射治疗剂有关. 这种方法将放射疗法传递给肿瘤细胞, enabling cancer cells to be destroyed in a more targeted manner than traditional external beam radiation, 为患者提供更有针对性的治疗.
Since the first US Food and Drug Administration (FDA) approvals of ADCs in 2000 and radioconjugates in 2018, 这些模式的发展进展迅速. 澳门第一赌城在线娱乐的愿景是看到他们重新定义未来的癌症治疗方案.
提高adc和放射性缀合物的靶特异性
adc和放射性缀合物能够重新定义癌症治疗领域, there is still work to be done – such as making them better at homing in on cancer cells and reducing off-target effects, 从而增强肿瘤特异性.
To achieve this, our focus is on continuous improvement of the design and engineering process. This includes how we identify novel targets using state-of-the-art multi-omics approaches, and using screening approaches which prioritise identifying drug candidates with functional effects early on in the drug discovery process. By combining diverse antibody generation approaches with advanced automation technologies, we are now able to identify novel antibody therapeutics at unprecedented speed and scale.
We also use sophisticated protein engineering to enhance tumour specificity by combining two different antibodies into one molecule, 称为双特异性抗体. Bispecific antibodies can bind to two different tumour associated antigens on the same cell simultaneously. 通过利用这个独特的性质, ADCs and radioconjugates can be made more selective to cancer cells than their traditional counterparts. This is because bispecific ADCs or radioconjugates can potentially deliver the payload to tumour cells that express both target antigens, leaving normal peripheral cells and tissue (which often only express one of the two antigens) unharmed.
We are also engineering better linkers to make our ADCs and radioconjugates more targeted. Unstable linkers can lead to ADCs dropping their payload prematurely in places where they can affect healthy tissue. Making them more stable ensures they carry their payloads all the way into tumour cells. 另一个重点是确保连接体只能在肿瘤细胞中被切割, 所以有效载荷只在癌细胞中被激活, 如果药物被健康组织吸收，它们就会保持失活状态.
建立一个有效载荷工具箱来匹配疾病生物学
无论ADC或无线电共轭有多精确, 没有有效载荷，它无法治疗癌症, 并不是所有的有效载荷对所有肿瘤的影响都是一样的. Therefore, we are working on matching ADC and radioconjugate payloads to the biology of the cancer cells, 目的是使癌症治疗更有效.
A common challenge with matching payloads to cancers is that tumours can be highly complex and diverse. 只针对一种生物机制的疗法可以暂时治疗癌症, 但是经常会出现抵抗, 肿瘤复发了. 为了解决这个问题，澳门第一赌城在线娱乐正在探索在一个ADC上使用多个不同的有效负载. 通过同时使用不同的作用机制, it could be possible to reduce drug resistance in tumours and provide more durable benefits for patients.
澳门第一赌城在线娱乐还设计了一些方法来扩大目标, cytotoxic impact of ADC payloads in a heterogenous tumour through the so-called bystander effect. This occurs when a payload is designed to kill nearby target negative cancer cells that could not initially be targeted by the ADC treatment.
adc和放射性缀合物的潜力无限
Our ADC and radioconjugate platforms are only the first step in our journey to redefine cancer therapies. We are excited about the potential of combining these platforms with other treatment modalities.
For example, we are exploring delivering them with therapies with different mechanisms of action such as 癌症免疫疗法 或者靶向DNA损伤反应途径的分子, or even combinations of different ADCs and/or radioconjugates that will be dosed sequentially.
澳门第一赌城在线娱乐的转型技术，比如蛋白质组学，人工智能和 计算病理学 也在帮助澳门第一赌城在线娱乐 加速这些新型治疗组合的发展. In some cases, they let us investigate which antibody target is most likely to work for a particular cancer or which patients are most likely to benefit.
We aim to continue to leverage these technologies in a way that in the future we can address multiple aspects of development simultaneously. 随着澳门第一赌城在线娱乐设计ADC和无线电共轭平台的能力不断发展, 澳门第一赌城在线娱乐开发针对正确药物的精准药物的能力也将如此, 给正确的病人, at the right time.
澳门第一赌城在线娱乐期待着看到澳门第一赌城在线娱乐的项目在未来几年如何发挥作用, 并继续致力于这一领域的持续创新.
