免疫治療
免疫治療 | |
---|---|
MeSH | D007167 |
OPS-301 | 8-03 |
免疫治療(英語:Immunotherapy),是指通過誘導、增強或抑制免疫反應的疾病治療方法[1]。其中旨在引起或增強免疫反應的免疫療法,稱為激活免疫療法(activation immunotherapies),而減少或抑制免疫反應則是抑制免疫療法(suppression immunotherapies)。
免疫療法往往比現有藥物的副作用少,包括減少對微生物疾病的抗藥性反應[2]。
基於細胞的免疫療法對一些癌症有效。免疫效應細胞如淋巴細胞、巨噬細胞、樹突狀細胞、自然殺手細胞(NK細胞),細胞毒性T淋巴細胞(CTL)等,通過針對腫瘤細胞表面的異常抗原,來共同幫助身體抵禦癌症。
粒細胞集落刺激因子(G-CSF)、干擾素、咪喹莫特與細菌細胞膜組分等療法,已經許可進入臨床治療。其他研究有白細胞介素-2、白細胞介素-7、白細胞介素-12、各種趨化因子、人工合成的CpG寡去氧核苷酸和葡聚糖等,這些均已進入臨床和臨床前研究。
免疫調節劑
[編輯]免疫調節劑是一類用於免疫療法的調節劑,包括各種重組、合成和天然的製劑。
調節劑 | 例子 |
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白細胞介素 | IL-2、IL-7、IL-12 |
細胞因子 | 干擾素、粒細胞集落刺激因子 |
趨化因子 | CCL3、CCL26、CXCL7 |
其他 | CpG寡去氧核苷酸、葡聚糖、咪喹莫特 |
激活免疫療法
[編輯]癌症
[編輯]癌症免疫療法通過刺激免疫系統來摧毀腫瘤。實踐、研究和實驗中有一系列策略方法。隨機對照研究報告顯示,不同類型癌症的免疫治療中,患者的生存期和無病期都有顯著提高[3][4][5][6],與常規治療方法聯合更會增加20%-30%的療效。
以粒細胞集落刺激因子刺激從病人血液中提取的外周血幹細胞產生淋巴細胞,在體外與腫瘤抗原共培養後輸回病人體內,並輔以刺激性的細胞因子增強免疫效應[7],該細胞可以摧毀攜帶相同抗原的腫瘤細胞[8]。
卡介苗免疫治療已證明對淺表性膀胱癌患者有效[9],通過灌輸入膀胱減弱活性的細菌,成功預防高達三分之二的復發案例。
局部免疫療法是利用免疫增強霜(咪喹莫特)產生干擾素,促使患者的殺手T細胞摧毀疣[10]、光化性角化病、基底細胞癌、陰道上皮內瘤樣病變[11]、鱗狀細胞癌[9][12]、皮膚淋巴瘤[13]和淺表惡性黑色素瘤[14]。
注射免疫治療包括流行性腮腺炎、念珠菌、HPV疫苗[15][16]或髮癬菌抗原注射劑(以治療尖銳濕疣)。
樹突狀細胞刺激
[編輯]醫學家可以通過刺激樹突狀細胞,激活對抗原的細胞毒性反應。樹突狀細胞是一種從患者體內獲取的抗原提呈細胞。它們可通過與抗原脈衝或與病毒載體轉染,使其顯現抗原。這些活性細胞在注入患者體內後,能夠標註出淋巴細胞的抗原(CD4+輔助性T細胞、細胞毒性T細胞和B細胞)。它隨後啟動細胞毒性抗腫瘤免疫反應,以對抗呈現出抗原的腫瘤細胞(適應性反應已經啟動)[18]。癌症疫苗Sipuleucel-T即採用該方法[19]。
T細胞過繼轉移
[編輯]過繼細胞轉移體外通過培育自體T細胞以備回輸[20]。該T細胞可能已經靶向腫瘤細胞;或者通過轉基因技術引導而生。這些T細胞被稱之為腫瘤浸潤性淋巴細胞,他們與高濃度的白細胞介素-2、抗CD3和同種異體反應性細胞融合。隨後一併轉移到患者體內,隨着白細胞介素-2藥效而進一步提高其抗癌活性。
在注入前需要進行受體的淋巴細胞缺失,即消除調節性T細胞以及未修改的內源性淋巴細胞;後者會和轉移細胞產生細胞穩態因子競爭[20][21][22][23]。淋巴細胞缺失可以通過實現全身照射實現[24]。在許多案例中,轉移細胞增多會伴生外周血,在注射後6-12個月內,T細胞的CD8指標水平會高達75%+[25]。2012年,轉移性黑色素瘤的臨床試驗正在多處進行[26]。
免疫增強療法
[編輯]自體免疫增強療法是利用患者的外周血來源自然殺手細胞、細胞毒性T淋巴細胞和其他免疫相關細胞,進行擴容後回輸[27]。該療法已被用於丙肝[28][29][30]、慢性疲勞綜合症[31][32]和人類疱疹病毒6型感染的試驗中[33]。
轉基因T細胞
[編輯]轉基因T細胞是一類轉基因技術。通過提取患者體內感染逆轉錄病毒的細胞,其包含一份T細胞受體(TCR)基因,用於專門識別腫瘤抗原。病毒結合了受體T細胞的基因組,細胞因此擴大非特異性和/或刺激。然後將細胞回輸到患者體內,產生對腫瘤細胞的免疫反應[34]。該技術已在難治性IV期的轉移性黑色素瘤[20]和加速期皮膚癌的案例中試驗[35][36][37]。
免疫功能恢復
[編輯]免疫療法的另一個潛在應用是恢復免疫功能缺陷患者的免疫系統。細胞因子、白細胞介素-7和白細胞介素-2已進行臨床試驗。
疫苗
[編輯]抗微生物劑免疫治療,包括接種疫苗,涉及激活免疫系統以應對傳染性病原體。
抑制免疫療法
[編輯]抑制免疫療法,是抑制自體免疫疾病中的異常免疫反應,或者降低正常免疫反應以阻止細胞或者器官移植中的排斥反應。
免疫抑制藥物
[編輯]免疫抑制藥物可以幫助控制器官移植和自體免疫性疾病。免疫反應依賴於淋巴細胞增殖,基於此免疫抑制劑用於抑制細胞生長。糖皮質激素是一類特定的淋巴細胞活化的抑制劑,而免疫親和素抑制劑則針對於T淋巴細胞活化目標;免疫抗體針對免疫反應的階段程度;其他藥物調節免疫反應。
免疫耐受
[編輯]人體機能不會天然地對自身組織發動免疫系統攻擊。免疫耐受療法尋求重建免疫系統,在自體免疫疾病或接受器官移植情況中,使身體停止錯誤地攻擊自己的器官[38]。並生成免疫力耐受或消除終身免疫抑制及伴生的副作用。它已經在器官移植、1型糖尿病或其他自體免疫性疾病中進行測試。
過敏
[編輯]免疫療法可用於治療過敏。儘管過敏治療(如抗組胺藥或皮質類固醇)可以進行治療過敏症狀,免疫治療也可以降低靈敏度過敏原,減輕嚴重過敏反應。
免疫治療可以產生長期效果[39]。免疫治療在一些患者中部分有效、或者一類患者完全無效,但它提供了減少或停止患者過敏症狀的機會。
該療法適用於有極度過敏或無法避免具體過敏原的患者。免疫療法一般不用於食品或藥物過敏。這種療法的人對過敏性鼻炎或哮踹特別有用。在免疫治療中的第一劑,增加微小的過敏原或抗原量。隨着時間的推移增加劑量,患者逐漸消除過敏性。這項技術已用於嬰兒疫苗,預防花生過敏[40]。
驅蟲療法
[編輯]豬鞭蟲(一類鞭蟲)和美洲鈎蟲已經用於免疫性疾病和過敏反應的測試。驅蟲治療已被視為一類緩解多發性硬化症[41]、克羅恩病[42][43][44]、過敏和哮喘的治療方法[45]。此類蠕蟲的免疫反應調節機制仍屬未知。醫學家推測它是重新極化的Th1/Th2免疫應答[46],或者樹突狀細胞功能的調節[47][48]。該類蠕蟲通過下調促炎性Th1細胞因子、白細胞介素12(IL-12)、γ-干擾素(IFN-γ)和腫瘤壞死因子(TNF-ά),促進生產調節Th2細胞因子(比如IL-10,IL-4,IL-5和IL-13)[46][49]。
此類蠕蟲的共同演化過程,產生了一些基因相關的白細胞介素表達和免疫性障礙(如克羅恩病,潰瘍性結腸炎和乳糜瀉)。
參見
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外部連結
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