免疫治疗

免疫治疗（英語：Immunotherapy），是指通过诱导、增强或抑制免疫反应的疾病治疗方法。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。 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、自然杀手细胞（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寡脱氧核苷酸和葡聚糖等，这些均已进入临床和临床前研究。 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。 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，与常规治疗方法联合更会增加20%-30%的疗效。 以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，该细胞可以摧毁携带相同抗原的肿瘤细胞。 卡介苗免疫治疗已证明对浅表性膀胱癌患者有效，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细胞摧毁疣、光化性角化病（英语：actinic keratoses）、基底细胞癌、阴道上皮内瘤样病变、鳞状细胞癌、皮肤淋巴瘤和浅表恶性黑色素瘤。 注射免疫治疗包括流行性腮腺炎、念珠菌、HPV疫苗或发癣菌（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。 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）。癌症疫苗Sipuleucel-T（英语：Sipuleucel-T）即采用该方法。 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。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。淋巴细胞缺失可以通过实现全身照射实现。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%+。2012年，转移性黑色素瘤的临床试验正在多处进行。 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手细胞、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。该疗法已被用于丙肝、慢性疲劳综合征和人类疱疹病毒6型（英语：HHV6）感染的试验中。 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。该技术已在难治性IV期的转移性黑色素瘤和加速期皮肤癌的案例中试验。 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）和白细胞介素-2已进行临床试验。 抗微生物剂免疫治疗，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，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。 免疫抑制药物可以帮助控制器官移植和自體免疫性疾病。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。 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。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型糖尿病或其他自體免疫性疾病中进行测试。 免疫疗法可用于治疗过敏。尽管过敏治疗（如抗组胺药或皮質類固醇）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。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或哮踹特别有用。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。 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、克罗恩病、过敏和哮喘的治疗方法。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，或者树突状细胞功能的调节。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（TNF-ά），促进生产调节Th2细胞因子（比如IL-10，IL-4，IL-5和IL-13）。 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，溃疡性结肠炎和乳糜泻）。 生物反应调节剂（英语：Biological response modifiers） 白细胞介素免疫治疗 微移植（英语：Microtransplantation） immunotherapies definition. 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PMID 19120496. doi:10.1111/j.1365-2567.2008.03008.x.  Fumagalli M, Pozzoli U, Cagliani R, Comi GP, Riva S, Clerici M, Bresolin N, Sironi M. Parasites represent a major selective force for interleukin genes and shape the genetic predisposition to autoimmune conditions. J. Exp. Med. June 2009, 206 (6): 1395–408. PMC 2715056 . PMID 19468064. doi:10.1084/jem.20082779.  "Cancer Miracles" （页面存档备份，存于互联网档案馆） Forbes article International Society for Biological Therapy of Cancer （页面存档备份，存于互联网档案馆） Cancer Research Institute Annual International Cancer Immunotherapy Symposia Series（页面存档备份，存于互联网档案馆） 中大發現新方法將肝腫瘤由「冷」轉「熱」 激活免疫T細胞滅癌 助發展更有效的新免疫療法 （页面存档备份，存于互联网档案馆） 生物主题 医学主题