开创了新一代免疫疗法

LAST UPDATED:
20 May 2024


Written by:

Simon Dovedi

澳门在线赌城娱乐IO Discovery的执行董事,主管

Saso Cemerski

澳门在线赌城娱乐(AstraZeneca)执行董事,免疫参与部主管

Corinne Cayatte

Senior Director, R&D肿瘤学,澳门在线赌城娱乐

Immuno-oncology has grown exponentially over the last decade and is transforming outcomes for patients. At AstraZeneca, we are exploring innovative ways to empower the body’s immune system to fight cancer, 例如新型多特异性抗体和下一代免疫细胞接合物, 包括澳门第一赌城在线娱乐开创性的三特异性CD8+选择性t细胞接合器平台.

免疫肿瘤学的扩展 

The first wave of immunotherapies has been transformative - potentially curative - for some patients, 但它们并不是对每个人都有效.Some cancers do not respond to immunotherapy, while others develop resistance over time.1

有许多因素影响的有效性 免疫疗法治疗, 比如病人的免疫系统状态和肿瘤微环境, 这两者都可以被癌细胞操纵来抑制免疫反应.2

澳门在线赌城娱乐澳门第一赌城在线娱乐的科学家正在探索 复杂的方法 来支持病人自身对抗癌症的免疫反应. These include novel ways to generate a synthetic immune response in patients whose immune system cannot recognise cancer and to overcome the immunosuppressive nature of the tumour microenvironment that limits the effectiveness of immunotherapy in some patients. 

It all leads to our ultimate goal of extending the impact of immunotherapy to more patients and overcoming mechanisms of resistance to 免疫疗法治疗s to help achieve our ambition of eliminating cancer as a cause of death.

了解下一代免疫疗法, 比如多特异性抗体和免疫细胞接合物, 可以利用身体的免疫系统来瞄准这个视频中的癌细胞:


多特异性抗体的进化

一些最有希望的免疫疗法包括 multispecific抗体 它们与多种不同的抗原结合,要么在相同的细胞上,要么在不同的细胞上.3

Bispecific antibodies can be used to generate new biological responses by targeting two molecules simultaneously. For example, they can be designed to target two different immune checkpoints on the same T cell, 将两种药物的潜在益处结合在一个分子中.4 Alternatively, multispecifics can be engineered to increase the potency and selectivity of a molecule, for example, by using one arm of the antibody to ‘guide’ the binding of the other arm to another receptor.4 Moreover, they can be engineered to deliver novel biology either through triggering non-canonical signalling cascades inside the target cell or by causing cells to interact in new ways.5

免疫细胞接合体的出现

The first generation of immunotherapies work by releasing the ‘brakes’ that control T cell function, 使它们能够攻击肿瘤细胞.6 But this relies on the presence of a pool of T cells that can recognise the abnormal antigens expressed on the surface of cancer cells.6

免疫细胞接合物 are a class of multispecific抗体 that bypass this requirement for antigen-specific T cells.7 抗体的一只手臂与癌细胞表面的目标结合, while the other binds to a receptor on the surface of an immune cell such as a T cell and brings the two into close proximity.7 This forms a synthetic synapse between them, activating the T cell to attack the cancer.7

This exciting modality offers a novel way to boost the patient’s immune system by tapping into a larger pool of immune cells than traditional immunotherapies. 它们甚至可以被设计成招募其他免疫细胞来攻击癌症.7 By generating a new response these approaches have potential benefits in patients with a weak or absent anti-tumour response.

第一代免疫细胞接合体是双特异性的, and have achieved considerable success in engaging the wider immune system by targeting CD3, 是由所有T细胞表达的吗.8 澳门第一赌城在线娱乐正在推进澳门第一赌城在线娱乐的新型三特异性CD8+选择性t细胞接合器平台, 其中包括几种优先与CD8+ T细胞结合的T细胞接合物, a sub-group of T cells with important roles in the prevention and elimination of cancer. Additionally, 这些t细胞接合物只有在与癌细胞结合时才有活性, 这意味着不必要的影响被最小化.

开发新一代免疫疗法

澳门第一赌城在线娱乐在多样化的肿瘤学投资组合上投入了大量资金, 它涵盖了许多不同的治疗方式. This lets us design and test novel combination therapies that can synergise with our multispecific antibody and immune cell engager candidates.

例如,澳门第一赌城在线娱乐正在探索使用 抗体-药物偶联物 还有可以选择性杀死癌细胞的小分子, 并结合免疫疗法启动抗肿瘤反应.9 This means that we can come at cancer from multiple angles to hit the tumour smarter and drive deeper and more durable responses.9

澳门第一赌城在线娱乐展望未来, we are continually advancing our understanding of how the immune system recognises and engages with tumour cells, to inform new ways to amplify the body’s natural defences against all types of cancer. 澳门第一赌城在线娱乐武器库中的一个关键工具是 先进的肿瘤学数据平台, which organises our vast data reserves and uses artificial intelligence to guide the development of novel therapeutics and strategies in oncology.

澳门第一赌城在线娱乐才刚刚开始

We are living through an era where immunotherapy has moved to the forefront of cancer treatment. We are tirelessly working to discover novel cancer treatments and look forward to a time when we are able to apply these innovative approaches to transform outcomes for more patients worldwide.


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References

1. Eno J. 多年来的免疫疗法. J Adv Pract Oncol. 2017;8(7):747-753.

2. Koury J, Lucero M, Cato C,等. 免疫疗法:利用免疫系统治疗癌症. J Immunol Res. 2018.

3. Suurs FV, Hooge MNL, de Vries EGE,等. A Review of Bispecific Antibodies and Antibody Constructs in Oncology and Clinical Challenges. Pharmacology & Therapeutics. 2019;201:103–19.

4. Ordóñez-Reyes C, Garcia-Robledo JE, Chamorro DF,等. Bispecific Antibodies in Cancer Immunotherapy: A Novel Response to an Old Question. Pharmaceutics. 2022;14(6):1243.

5. 李国强,张勇,苏勇,等. 细胞型特异性强效Wnt信号阻断双特异性抗体. Sci Rep. 2018;8(1):766.

6. Huehls A M, et al. 癌症免疫治疗中的双特异性T细胞接合物. Immunol Cell Biol. 2015; 93(3): 290-296.

7. 冯建军,张建军,张建军,等. 免疫细胞接合物 in solid tumors: promises and challenges of the next generation immunotherapy. ESMO Open. 2021;6(1):100046.

8. 周松,刘敏,任峰,等. 双特异性T细胞参与癌症治疗的前景. Biomark Res. 2021;9(1):38.

9. Peters C, Brown S. 抗体-药物偶联物作为新型抗癌化疗药物. Biosci Rep. 2015;35(4):e00225.


Veeva ID: Z4-63995
筹备日期:2024年5月