免疫治疗

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免疫治疗
介入手段
MeSH D007167
OPS-301 code 8-03

免疫治疗英语:Immunotherapy),是指通过诱导、增强或抑制免疫反应的疾病治疗方法[1]。其中旨在引起或增强免疫反应的免疫疗法,称为激活免疫疗法activation immunotherapies),而减少或抑制免疫反应则是抑制免疫疗法suppression immunotherapies)。

免疫疗法往往比现有药物的副作用少,包括减少对微生物疾病的抗药性反应[2]

基于细胞的免疫疗法对一些癌症有效。免疫效应细胞如淋巴细胞巨噬细胞树突状细胞自然杀伤细胞(NK细胞),细胞毒性T淋巴细胞(CTL)等,通过针对肿瘤细胞表面的异常抗原,来共同帮助身体抵御癌症。

粒细胞集落刺激因子英语granulocyte colony-stimulating factor(G-CSF)、干扰素咪喹莫特英语imiquimod与细菌细胞膜组分等疗法,已经许可进入临床治疗。其他研究有白细胞介素-2白细胞介素-7英语Interleukin-7白细胞介素-12英语Interleukin-12、各种趋化因子、人工合成的CpG寡脱氧核苷酸葡聚糖等,这些均已进入临床和临床前研究。

免疫调节剂[编辑]

免疫调节剂是一类用于免疫疗法的调节剂,包括各种重组、合成和天然的制剂。

调节剂 例子
白细胞介素 IL-2IL-7英语Interleukin 7IL-12英语Interleukin 12
细胞因子 干扰素粒细胞集落刺激因子英语G-CSF
趋化因子 CCL3英语CCL3CCL26英语CCL26CXCL7
其他 CpG寡脱氧核苷酸葡聚糖咪喹莫特英语Imiquimod

激活免疫疗法[编辑]

癌症[编辑]

癌症免疫疗法通过刺激免疫系统来摧毁肿瘤。实践、研究和实验中有一系列策略方法。随机对照研究报告显示,不同类型癌症的免疫治疗中,患者的生存期和无病期都有显著提高[3][4][5][6],与常规治疗方法联合更会增加20%-30%的疗效。

粒细胞集落刺激因子英语Granulocyte colony-stimulating factor刺激从病人血液中提取的外周血干细胞产生淋巴细胞,在体外与肿瘤抗原共培养后输回病人体内,并辅以刺激性的细胞因子增强免疫效应[7],该细胞可以摧毁携带相同抗原的肿瘤细胞[8]

卡介苗免疫治疗已证明对浅表性膀胱癌患者有效[9],通过灌输入膀胱减弱活性的细菌,成功预防高达三分之二的复发案例。

局部免疫疗法是利用免疫增强霜(咪喹莫特英语imiquimod)产生干扰素,促使患者的杀手T细胞摧毁[10]光化性角化病英语actinic keratoses基底细胞癌英语basal cell cancer阴道上皮内瘤样病变[11]鳞状细胞癌[9][12]、皮肤淋巴瘤[13]和浅表恶性黑色素瘤[14]

注射免疫治疗包括流行性腮腺炎、念珠菌、HPV疫苗[15][16]发癣菌英语trichophytin抗原注射剂(以治疗尖锐湿疣)。

过继细胞转移英语Adoptive cell transfer疗法已在肺癌和其他癌症中进行测试[17]

树突状细胞刺激[编辑]

医学家可以通过刺激树突状细胞,激活对抗原的细胞毒性反应。树突状细胞是一种从患者体内获取的抗原提呈细胞。它们可通过与抗原脉冲或与病毒载体转染,使其显现抗原。这些活性细胞在注入患者体内后,能够标注出淋巴细胞的抗原(CD4+辅助性T细胞细胞毒性T细胞和B细胞)。它随后启动细胞毒性抗肿瘤免疫反应,以对抗呈现出抗原的肿瘤细胞(适应性反应已经启动)[18]癌症疫苗Sipuleucel-T英语Sipuleucel-T即采用该方法[19]

T细胞过继转移[编辑]

过继细胞转移英语Adoptive cell transfer体外通过培育自体T细胞以备回输[20]。该T细胞可能已经靶向肿瘤细胞;或者通过转基因技术引导而生。这些T细胞被称之为肿瘤浸润性淋巴细胞英语tumor-infiltrating lymphocyte,他们与高浓度的白细胞介素-2、抗CD3和同种异体反应性细胞融合。随后一并转移到患者体内,随着白细胞介素-2药效而进一步提高其抗癌活性。

在注入前需要进行受体的淋巴细胞缺失,即消除调节性T细胞以及未修改的内源性淋巴细胞;后者会和转移细胞产生细胞稳态因子竞争[20][21][22][23]。淋巴细胞缺失可以通过实现全身照射实现[24]。在许多案例中,转移细胞增多会伴生外周血,在注射后6-12个月内,T细胞的CD8指标水平会高达75%+[25]。2012年,转移性黑色素瘤的临床试验正在多处进行[26]

免疫增强疗法[编辑]

自体免疫增强疗法英语Autologous immune enhancement therapy是利用患者的外周血来源自然杀伤细胞、细胞毒性T淋巴细胞和其他免疫相关细胞,进行扩容后回输[27]。该疗法已被用于丙肝[28][29][30]慢性疲劳综合征[31][32]人类疱疹病毒6型英语HHV6感染的试验中[33]

转基因T细胞[编辑]

转基因T细胞英语Genetically engineered T cell是一类转基因技术。通过提取患者体内感染逆转录病毒的细胞,其包含一份T细胞受体(TCR)基因,用于专门识别肿瘤抗原。病毒结合了受体T细胞的基因组,细胞因此扩大非特异性和/或刺激。然后将细胞回输到患者体内,产生对肿瘤细胞的免疫反应[34]。该技术已在难治性IV期的转移性黑色素瘤[20]和加速期皮肤癌的案例中试验[35][36][37]

免疫功能恢复[编辑]

免疫疗法的另一个潜在应用是恢复免疫功能缺陷患者的免疫系统。细胞因子白细胞介素-7英语Interleukin-7白细胞介素-2已进行临床试验。

疫苗[编辑]

抗微生物英语Anti-microbial免疫治疗,包括接种疫苗,涉及激活免疫系统以应对传染性病原体。

抑制免疫疗法[编辑]

抑制免疫疗法,是抑制自体免疫疾病中的异常免疫反应,或者降低正常免疫反应以阻止细胞或者器官移植中的排斥反应

免疫抑制药物[编辑]

免疫抑制药物可以帮助控制器官移植和自身免疫性疾病。免疫反应依赖于淋巴细胞增殖,基于此免疫抑制剂用于抑制细胞生长。糖皮质激素是一类特定的淋巴细胞活化的抑制剂,而免疫亲和素抑制剂则针对于T淋巴细胞活化目标;免疫抗体针对免疫反应的阶段程度;其他药物调节免疫反应。

免疫耐受[编辑]

人体机能不会天然地对自身组织发动免疫系统攻击。免疫耐受疗法寻求重建免疫系统,在自体免疫疾病或接受器官移植情况中,使身体停止错误地攻击自己的器官[38]。并生成免疫力耐受或消除终身免疫抑制及伴生的副作用。它已经在器官移植、1型糖尿病或其他自身免疫性疾病中进行测试。

过敏[编辑]

免疫疗法可用于治疗过敏。尽管过敏治疗(如抗组胺药皮質類固醇)可以进行治疗过敏症状,免疫治疗也可以降低灵敏度过敏原,减轻严重过敏反应。

免疫治疗可以产生长期效果[39]。免疫治疗在一些患者中部分有效、或者一类患者完全无效,但它提供了减少或停止患者过敏症状的机会。

该疗法适用于有极度过敏或无法避免具体过敏原的患者。免疫疗法一般不用于食品或药物过敏。这种疗法的人对过敏性鼻炎哮踹特别有用。在免疫治疗中的第一剂,增加微小的过敏原或抗原量。随着时间的推移增加剂量,患者逐渐消除过敏性。这项技术已用于婴儿疫苗,预防花生过敏[40]

驱虫疗法[编辑]

猪鞭虫(一类鞭虫)和美洲钩虫英语Hookworm已经用于免疫性疾病和过敏反应的测试。驱虫治疗英语Helminthic therapy已被视为一类缓解多发性硬化症[41]克罗恩病[42][43][44]、过敏和哮喘的治疗方法[45]。此类蠕虫的免疫反应调节机制仍属未知。医学家推测它是重新极化的Th1/Th2免疫应答[46],或者树突状细胞功能的调节[47][48]。该类蠕虫通过下调促炎性Th1细胞因子、白细胞介素12(IL-12)、γ-干扰素(IFN-γ)和肿瘤坏死因子英语Tumour Necrosis Factor(TNF-ά),促进生产调节Th2细胞因子(比如IL-10,IL-4,IL-5和IL-13)[46][49]

此类蠕虫的共同演化过程,产生了一些基因相关的白细胞介素表达和免疫性障碍(如克罗恩病,溃疡性结肠炎乳糜泻)。

参见[编辑]

参考[编辑]

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