免疫治療

针对机体异常的免疫功能,利用物理、化学和生物学等手段及免疫学原理,通过人为地增强或抑制机体的免疫功能,从而达到治疗疾病目标的措施

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)。

免疫治療
MeSHD007167
OPS-301英語OPS-3018-03

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英語granulocyte colony-stimulating factor(G-CSF)、干擾素咪喹莫特英語imiquimod與細菌細胞膜組分等療法,已經許可進入臨床治療。其他研究有白血球介素-2白血球介素-7白血球介素-12英語Interleukin-12、各種趨化因子、人工合成的CpG寡脫氧核苷酸葡聚糖等,這些均已進入臨床和臨床前研究。

免疫調節劑

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
白血球介素 IL-2IL-7IL-12英語Interleukin 12
細胞因子 干擾素粒細胞集落刺激因子英語G-CSF
趨化因子 CCL3英語CCL3CCL26英語CCL26CXCL7
其他 CpG寡脫氧核苷酸葡聚糖咪喹莫特英語Imiquimod

激活免疫療法

癌症

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。

粒細胞集落刺激因子英語Granulocyte colony-stimulating factor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(咪喹莫特英語imiquimod)產生干擾素,促使患者的殺手T細胞摧毀[10]光化性角化病英語actinic keratoses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]髮癬菌英語trichophytin抗原注射劑(以治療尖銳濕疣)。

過繼細胞轉移英語Adoptive cell transfer療法已在肺癌和其他癌症中進行測試[17]

樹突狀細胞刺激

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英語Sipuleucel-T即採用該方法[19]

T細胞過繼轉移

過繼細胞轉移英語Adoptive cell transfer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英語tumor-infiltrating lymphocyte,他們與高濃度的白血球介素-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,隨著白血球介素-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

自體免疫增強療法英語Autologous immune enhancement therapy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C肝[28][29][30]慢性疲勞症候群[31][32]人類疱疹病毒6型英語HHV6感染的試驗中[33]

轉基因T細胞

轉基因T細胞英語Genetically engineered T cell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

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。細胞因子白血球介素-7白血球介素-2已進行臨床試驗。

疫苗

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

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

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

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

免疫療法可用於治療過敏。儘管過敏治療(如抗組胺藥皮質類固醇)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。隨著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

豬鞭蟲(一類鞭蟲)和美洲鉤蟲英語Hookworm已經用於免疫性疾病和過敏反應的測試。驅蟲治療英語Helminthic therapy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、白血球介素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血球介素表達和免疫性障礙(如克羅恩病,潰瘍性結腸炎乳糜瀉)。

參見

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