探索癌症

PD-1抑制劑與PD-L1抑制劑有何不同? 相信是許多人的疑問 希望這篇能對您有些幫助

建議您先讀 腫瘤是如何抑制抗癌免疫反應的 和 什麼是CTLA4 ? 什麼是PD1? 會比較能夠理解這篇的內容

作用的對象不同

PD-1抑制劑作用於所有呈現PD-1受體的細胞 PD-1受體通常呈現於活化的T細胞 因此所有活化的T細胞都可能受到PD-1抑制劑的影響

PD-L1抑制劑作用於所有呈現PD-L1受體的細胞  PD-L1受體通常呈現於腫瘤與腫瘤微環境裡的免疫細胞以及調節型T細胞

Anti PD1藥品 對多數人而言 附作用比化療輕許多

Anti PD1藥品雖然毒性低 但是卻有可能會造成嚴重問題 威脅生命甚至導致死亡

我的朋友肺腺癌4期就是打OPDIVO (Nivolumab)造成肝腎衰竭去世的

所以Anti PD1藥品的安全性

PD-1抑制劑能夠作用於所有活化的T細胞

癌症擴散與腫瘤能夠抑制抗癌免疫反應息息相關

一旦腫瘤能抑制抗癌免疫反應從此身體裡再也沒有可以阻止它擴散的力量

所有罹癌的朋友的免疫系統都無法對體內的癌症產生有效免疫反應(清除癌細包)

即使你現在的吃的健康 有充足睡眠 也有運動 不常感冒 有感冒也很快能痊癒

你的免疫系統是運作正常的 能有效清除外來的細菌病毒

FDA核准上市全球首支anti PDL1藥品Tecentriq (atezolizumab)治療4期肺腺癌

不論病人腫瘤是否呈現PDL1

FDA 核准使用Tecentriq (atezolizumab) 治療化療或EGRF 或ALK 標靶治療失效的病人

FDA根據二期與隨機分配三期臨床實驗結果做出上述決定

Tecentriq 比較鉑金類化療藥物能延長病人存活期平均中間值4.2個月達到中位數13.8個月

毒殺型T細胞是抗病毒與癌症的主力

T細胞被激活的過程上面有談到

每個T細胞只對一種抗原起反應

因此T細胞對於抗原俱有專一性

不會攻擊不俱有抗原的目標

DC Dendritic cells 是人體主要的抗原承現細胞

DC 吞噬病原體將消化後的病原體碎片(抗原)承現於細胞膜表面

回到淋巴結承現給T細胞與B細胞藉以激起適應性免疫反應

適應性免疫反應包括激活的B細胞轉變成漿細胞生產抗體

激活的T細胞轉變成 T helper 細胞毒殺型T細胞 和記憶型T細胞

Multiple randomized studies have demonstrated improved response rates, progression-free survival, and quality of life for treatment-naive, advanced-stage adenocarcinoma patients harboring sensitizing EGFR mutations when they are treated with tyrosine kinase inhibitor therapy, as compared with chemotherapy. Despite improved outcomes with these agents, the majority of patients will eventually develop resistance and subsequent clinical progression. Recently, there has been a firmer understanding of the molecular mechanisms of the resistance that develops as a consequence of treatment, most notably the identification of a second-site EGFR mutation, T790M. While this understanding can inform subsequent treatment decisions, disease progression can be heterogeneous, and there are several competing therapeutic options. Treatment decisions must consider this clinical heterogeneity, factoring in the pace of disease growth, lung cancer–related symptoms, and the potential presence of T790M mutations. Herein, we review the available literature addressing these competing strategies and attempt to clarify best treatment practices, including the emerging role of T790M-directed therapies.

http://www.cancernetwork.com/oncology-journal/attacking-moving-target-understanding-resistance-and-managing-progression-egfr-positive-lung-cancer/page/0/1

During the last few decades, significant efforts of the interaction between immune system and immunotherapy to NSCLC have been acquired. Recent data have indicated that the lack of immunologic control is recognized as a hallmark of cancer currently. Programmed death-1 (PD-1) and its ligand PD-L1 play a key role in tumor immune escape and the formation of tumor microenvironment, closely related with tumor generation and development. Blockading the PD-1/PD-L1 pathway could reverse the tumor microenvironment and enhance the endogenous antitumor immune responses.

重點節錄

Studies indicated that PD-1/PD-L1 pathway inhibitors were most effective when combined with treatments that activating the immune system.

Preclinical evidence exists for the complementary roles of CTLA-4 and PD-1 in regulating adaptive immunity, and this provides rationale for combining drugs targeting these pathways. In a Phase I study in 46 chemotherapy-naive patients with NSCLC, four cohorts of patients received ipilimumab (3 mg/kg) plus nivolumab for four cycles followed by nivolumab 3 mg/kg intravenously every 2 weeks. The ORR was 22% and did not correlate with PD-L1 status.

In another Phase I study, 56 patients with advanced NSCLC were assigned based on histology to four cohorts to receive nivolumab (5–10 mg/kg) intravenously every 3 weeks plus one of four concurrent standard “platinum doublet” chemotherapy regimens. No dose de-escalation was required for dose-limiting toxicity. The ORR was 33–50% across arms and the 1-year OS rates were promising at 59–87%.

鄭醫師的部落格

http://delightdetox1268.pixnet.net/blog/post/280267793-%E8%A6%8F%E5%BE%8B%E9%81%8B%E5%8B%95%E5%8F%AF%E4%BB%A5%E5%B9%AB%E5%8A%A9%E9%9B%8C%E6%BF%80%E7%B4%A0%E5%81%A5%E5%BA%B7%E4%BB%A3%E8%AC%9D%EF%BC%8C%E9%99%8D%E4%BD%8E%E4%B9%B3%E7%99%8C

Atezolizumab NSCLC第三期臨床實驗收ALK EGFR標靶化療失效的病人
全球共1225名病人 細節將在近期公布
http://www.roche.com/media/store/releases/med-cor-2016-09-01.htm
Atezolizumab NSCLC第三期臨床實驗顯示

羅氏藥廠公佈PDL1抑制劑atezolizumab與奈米太平洋紫杉醇併用治療三陰性乳癌數據

約三分之二的病人有反應 無論腫瘤是否有PD-L1表象

數據顯示PDL1抑制劑atezolizumab可以與奈米太平洋紫杉醇併用 加強免疫系統辨識和摧毀癌細胞的能力

反應率65% 其中以第一次化療的病人最高 為88.9%

56%的病人有3級或4級的不良事件 與單獨使用奈米太平洋紫杉醇的不良事件發生率類似

文 / 胡涵婷醫師 (血液與腫瘤內科)

筆者在美國重新接受住院醫師訓練時，親眼見證了癌症如何以野火燎原的攻勢，掠奪免疫機制被壓抑的病人的生命。我的訓練醫院內科副主任十多年前診斷早期大腸癌，開刀治癒了。後來，他因為一種罕見的膽道疾病造成肝衰竭，接受肝臟移植。雖然移植成功，他沉寂了超過十年的大腸癌，卻因為預防肝移植排斥所必須服用的免疫抑制劑，來勢洶洶地復發了。大腸癌細胞侵佔他的肺、骨頭以及甫移植的肝臟；短短三個月內，他就離開人世。這個活生生的例子告訴我們，人體有高度有效的控制癌細胞的免疫機制。當免疫機制崩潰或削弱時，癌症往往就一發不可收拾。
類似的故事實例與科學證據，比比皆是，一再說明了癌症與免疫機制的重要相關性。