写的:
丹尼尔•弗里曼
早期发展肿瘤学项目副总裁&D、澳门在线赌城娱乐
马克Cobbold
早期发展肿瘤学研发部副总裁&D、澳门在线赌城娱乐
马修·张春
副总裁，临床组负责人，早期发展肿瘤R&D、澳门在线赌城娱乐
近年来，澳门第一赌城在线娱乐看到免疫肿瘤学(IO)引起了很多兴奋。, 从临床的变革性成果到该领域先驱的诺贝尔奖.1,2,3
第一波IO疗法的目标是 克服免疫检查点 释放免疫系统对抗癌症的力量, 已经成为许多治疗方案的支柱, 与PD-1, PD-L1和CTLA-4抑制剂在许多肿瘤类型的常规临床应用.2 但是，虽然这些药物开辟了这一领域, not all patients respond to checkpoint inhibition and responses are not always as deep or durable as we might hope.
防御、忽视或攻击癌细胞
从历史上看, 药物开发的重点是针对肿瘤的分子特征, most notably the genetic mutations that have been identified as contributing to the growth and spread of 癌症 cells. 但癌症不仅仅是一种无赖病, mutated cells growing out of control: the presence of tumours themselves demonstrates how 癌症 cells can evade the immune processes that normally protect us by keeping aberrant cells in check.
免疫系统是人体的自然防御系统, responsible for responding to external pathogens such as bacteria and viruses and protecting us from abnormal internal disease processes like 癌症.4 T-cells and myeloid cells play a major role in this anti-癌症 response by recognising and eliminating tumour cells while leaving healthy cells unharmed.5,6 Immune checkpoints are a key part of the decision-making process that determines whether or not T-cells will attack, 并且可以被癌细胞操纵以逃避免疫反应.5
澳门第一赌城在线娱乐正在从两个角度解决免疫逃避的挑战. 首先, by finding novel ways to overcome the defensive mechanisms that tumours use to escape the immune system, progressing beyond PD-L1 blockade to explore the potential of targeting other immune checkpoints such as TIM-3 and GDF-15.
其次, 如果免疫细胞忽略了附近癌细胞的威胁, we’re searching for ways to create a more immunogenic environment around the tumour to alert the immune cells of the danger posed by the 癌症 cells.
破解免疫反应
基于抗体的检查点抑制剂通过 与免疫细胞表面的特定受体(或其配体)结合的如PD-1或CTLA-4.7 然而, because these receptors are also involved in the normal balance between surveillance and auto-immunity, disruption of checkpoint signalling pathways can lead to immune-related systemic side effects including damage to healthy tissue.8
为了克服这个问题, we are drawing on our long history of protein engineering to design bispecific antibodies that simultaneously target different immune checkpoints on the same cell. 通过将两种药物结合在一起, these dual-purpose antibodies could help to drive more durable responses in the clinic or overcome evolved resistance to blockade of the PD-1/PD-L1 axis.
展望未来, 澳门第一赌城在线娱乐正在探索重新引导不能识别癌症的t细胞的方法, 哪些物质比那些物质更丰富，更有效. 为此目的, t细胞衔接器, which direct T-cells to the tumour and amplify that patient’s own anti-癌症 immune response, 免疫肿瘤学是一个越来越受关注的领域吗.
澳门第一赌城在线娱乐正在探索免疫的不同方面, 包括调节其他免疫细胞的潜力, 比如骨髓细胞, 作为一种治疗癌症的方法. We are also looking at ways of manipulating the tumour microenvironment to make it more amenable for T cells to function, 通过 阻断像LIF这样的促癌分子 和CD73或by 加入细胞因子，如IL-12 促进抗肿瘤免疫反应.9,10
除此之外，创新的先进疗法，如 细胞疗法– engineered immune cells that can find and destroy 癌症 – are becoming increasingly important in 癌症 therapy.
Discover how we are activating the immune system using t细胞衔接器 to damage 癌症 cells and potentially help address hard-to-treat 癌症s in the below animation:
合适的药物，合适的病人，合适的时间
充分发挥免疫疗法的力量, we need not just new powerful medicines but also the insight to match each patient with the therapy that is most likely to work for them.
Our diverse portfolio of potential medicines lends itself to testing different combination treatment strategies. 例如, 将免疫疗法与旨在杀死癌细胞的药物相结合, 如抗体药物偶联物(adc), could lead to additive or synergistic responses as dying cells attract the attention of the immune system to further enhance the effect. We are also exploring the potential of combining drugs from our early pipeline with PD-L1 checkpoint inhibition to induce deeper and more durable anti-tumour responses.
Developing next-generation biomarkers will be important for stratifying patients and identifying the most appropriate treatment or combination therapy. By connecting deep understanding from biology with emerging data from patients in our early clinical trials, we can develop and test new hypotheses to discover which patients will benefit most from which treatments.
癌症越早得到诊断和治疗，越容易患上癌症 生存的机会更大.11 Every round of chemotherapy or radiotherapy can inflict damage on the immune system and result in more resistant 癌症 cells, 这使得这种疾病更难治疗，免疫系统的反应能力也更弱.12 Intervening early with rational combinations of targeted treatments and immunotherapy is likely to give patients the best chance of a cure.
免疫肿瘤学的未来
展望未来, it is exciting to think how immunotherapies could be combined with advances in the diagnostics space such as liquid biopsy, identifying the very earliest signs of 癌症 and activating the immune system to seek out and remove dangerous cells wherever they may be. And one day it may even be possible to manipulate the immune environment of the body to prevent 癌症 from developing in the first place.
