挺牛但是长期效果,尤其是复发情况有待观察(个人不太看好,为啥肿瘤一定要有免疫 原性??) 谁知道相关文章推荐一下。 Safety and Activity of Anti–PD-L1 Antibody in Patients with Advanced Cancer (NEJM 2012) Background: A major implication of the clinical activity of immune checkpoint blockade is that significant endogenous immune responses to tumor antigens are generated, and these responses may be harnessed therapeutically to mediate clinical tumor regression on checkpoint inhibition. An emerging concept in cancer immunology is that inhibitory ligands such as PD-L1 are induced in response to immune attack, a mechanism termed adaptive resistance. This potential mechanism of immune resistance by tumors suggests that therapy directed at blocking interaction between PD-1 and PD-L1 might synergize with other treatments that enhance endogenous antitumor immunity. Result: Blockade of the immune inhibitory ligand PD-L1 by a monoclonal antibody produced both durable tumor regression (objective response rate, 6 to 17%) and prolonged (≥24 weeks) disease stabilization in patients with metastatic non–small-cell lung cancer, melanoma, renal-cell cancer, and ovarian cancer. The objective response in 5 of 49 patients (10%) with advanced non–small-cell lung cancer was unexpected. Important feature: The durability of response across multiple tumor types was greater than that observed with most chemotherapies and kinase inhibitors used in these diseases, although no direct comparisons have been performed. Future direction: (1) Identify which patients are likely to have a response, to determine an appropriate clinical dose, and to define the spectrum of tumors in which targeting of this pathway will have antitumor effects. (2) Long term effect needs to be studied to confirm whether patients continue to have tumor control after cessation of blockade of the pathway between PD-1 and PD-L1. Such tumor control could reflect a persistent antitumor immune response and the generation of effective immunologic memory to enable sustained control of tumor growth.
【在 w***r 的大作中提到】 : 挺牛但是长期效果,尤其是复发情况有待观察(个人不太看好,为啥肿瘤一定要有免疫 : 原性??) : 谁知道相关文章推荐一下。 : Safety and Activity of Anti–PD-L1 Antibody in Patients with Advanced Cancer : (NEJM 2012) : Background: A major implication of the clinical activity of immune : checkpoint blockade is that significant endogenous immune responses to tumor : antigens are generated, and these responses may be harnessed : therapeutically to mediate clinical tumor regression on checkpoint : inhibition. An emerging concept in cancer immunology is that inhibitory
DC vaccine 做了这么多年还是没啥突破啊,provenge都快卖不去了。我觉得体外培养 的DC还是很难模拟体内DC。GM-CSF培养的DC在老鼠体内只有约5%迁移。 In vivo targeting DC 也做了很多年了吧,几乎所有发现的c-type lectin都试了,也 没见得有多少临床进展。本来想做做这块,感觉问题很多啊。
【在 d*p 的大作中提到】 : 国内临床上还是在用这个cik, cik+dc, cik 我前面讲了,这里就只讲一下dc。 : dc vaccine 的应用有两个主要问题, 一是dc既可以激活免疫反应,也可抑制免疫反应 : ,如何做到高效激活针对肿瘤抗原的免疫反应,还有很多工作要做,并不是简单地将体 : 外培养的dc与抗原混合就够了。二是缺乏有效的肿瘤抗原,这个与传统的肿瘤抗原鉴定 : 方法的低效率有关,国内很多地方就是用肿瘤细胞lysis的蛋白来做抗原,这里面有多 : 少是肿瘤抗原,你想想就知道了。 : dc vaccine 是非常有希望的一个方向,现在发展很快,改进方法也很多,未来5年左右 : 应该会有不少新的治疗性疫苗出现。而与现有其他治疗方法结合,也是大势所趋。 : : cells
【在 d*p 的大作中提到】 : David Mooney's implanted vaccine is a good example. They already started : clinical trial. : : 攻击
w*r
32 楼
肿瘤 的免疫原性是一定的,肿瘤的基因组和转录组都有非常大的变化,高通量测序也 表明, 不同病人的肿瘤,产生新蛋白的突变在20-100个左右。 Those mutations may not be presented to the immunosystem.That's why only a small fraction of patients benefit in the study you mentioned. Could you find a T cell clone reacting to mutant Ras? Moreover, decreased the immunocheckpoint has a threshold issue similar to chemotherapy, the dosage. 肿瘤就很难再通过突变来逃逸 this is an interesting point, but the assumption here is that all the tumor cells have to express multiple effective tumor antigens. the fact is that tumor are generally heterogenous. I believe that immunotherapy is one of the powerful weapons in the anti- cancer toolbox. But I don't think modulation of immunocheckpoint can conque cancer. As the article pointed out, identify tumor types responsive to immunotherapy is the next goal.
缺乏有效的抗原呈递,正是肿瘤强抑制环境的一个重要原因。当然并不是所有的突变都 能够成为抗原,因为免疫系统首先要避免攻击自身。也并不是非要突变才能形成肿瘤抗 原, immune privilege sites, embronic develpoment specific gene的异常表达, 都可形成肿瘤抗原。可以说,肿瘤本身并不缺乏抗原,缺的是一个形成免疫反应的环境。 NK cell mediated Killing, Antigen spreading, 都可以解释你的第二个问题。建议 你看看参与免疫反应的各类细胞,以及免疫反应的各个阶段和逐级放大的过程。
. tumor
【在 w***r 的大作中提到】 : 肿瘤 的免疫原性是一定的,肿瘤的基因组和转录组都有非常大的变化,高通量测序也 : 表明, : 不同病人的肿瘤,产生新蛋白的突变在20-100个左右。 : Those mutations may not be presented to the immunosystem.That's why only a : small fraction of patients benefit in the study you mentioned. Could you : find a T cell clone reacting to mutant Ras? Moreover, decreased the : immunocheckpoint has a threshold issue similar to chemotherapy, the dosage. : 肿瘤就很难再通过突变来逃逸 : this is an interesting point, but the assumption here is that all the tumor : cells have to express multiple effective tumor antigens. the fact is that
For all cell based therapies, one problem is to enhance DC/T cell activity in vivo. Carl June lab did good job to activate T cell. What about to DCs? drp, can you give me some good reference in "dc既可以激活免疫反应,也可抑制 免疫反应"? Can mature and activated DC also lead to 抑制免疫反应? Thanks in advance.
【在 d*p 的大作中提到】 : 国内临床上还是在用这个cik, cik+dc, cik 我前面讲了,这里就只讲一下dc。 : dc vaccine 的应用有两个主要问题, 一是dc既可以激活免疫反应,也可抑制免疫反应 : ,如何做到高效激活针对肿瘤抗原的免疫反应,还有很多工作要做,并不是简单地将体 : 外培养的dc与抗原混合就够了。二是缺乏有效的肿瘤抗原,这个与传统的肿瘤抗原鉴定 : 方法的低效率有关,国内很多地方就是用肿瘤细胞lysis的蛋白来做抗原,这里面有多 : 少是肿瘤抗原,你想想就知道了。 : dc vaccine 是非常有希望的一个方向,现在发展很快,改进方法也很多,未来5年左右 : 应该会有不少新的治疗性疫苗出现。而与现有其他治疗方法结合,也是大势所趋。 : : cells