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徐迎新:免疫细胞工程技术与抗肿瘤绿色医疗模式的建立
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徐迎新,现为301医院普通外科研究所副所长,全军普通外科医疗专科中心副主任。长期从事创伤、休克、脓毒症及多器官功能障碍综合症发病机制和防治研究。

尽管科学技术的发展日新月异,各国政府在生命科学领域的投入不断增加,但对于恶性肿瘤的治疗一直未能突破。从1975年到2005年这30年间,肿瘤的总体死亡率并没有发生太大的变化。人们不禁要问为什么许多肿瘤病人经历了手术、化疗、放疗所带来的种种痛苦,付出了昂贵的医疗费用,却未能明显地延长生命。肿瘤病人的希望在哪里?

肿瘤是一种慢性疾病,全身性疾病,且为多基因改变,其实质是体内突变细胞与免疫细胞之间的一场内部战争,二者的博弈贯穿医疗过程的始终,也决定了该个体的生存与否。同时人体局部的微环境,整体内环境,外部自然环境以及社会心理因素都对肿瘤的发生和预后产生重大影响。因此,恶性肿瘤决不是手术可以切的干净,放、化疗可以根治的。为探索新的医疗模式,本研究团队在国家“863”计划、国家自然科学基金和企业资金的资助下,经过十余年的探索和研究,以免疫细胞工程技术为切入点,并成功进行临床转化,走出了一条绿色抗癌的新路。

  1.建立肿瘤疫苗及多种人体免疫细胞(肿瘤抗原致敏DC、靶向肿瘤干细胞DC疫苗、DC诱导特异性T细胞、肿瘤浸润T细胞、引流区淋巴结T细胞、NK、CIK和B细胞)制备与体外扩增技术的研究与临床应用平台,以及适用于免疫细胞过继转移的疗效评价体系。在临床应用中不断进行打破DC耐受,降低Treg,抑制炎症反应等方面研究,以提高免疫细胞过继转移治疗的疗效。

  2. 我们尝试的抗肿瘤绿色医疗模式基于对肿瘤局部的积极处理与全身抗肿瘤免疫功能恢复/重建并举的理念,综合运用常规手术、各种微创技术、细胞工程技术、化疗和放疗。对于一位初诊肿瘤患者,首先进行个体化总体治疗方案的顶层设计,然后分步实施,系统跟踪。1)通过外科及其它微创技术,或适当方式与剂量的放疗,最大限度减少肿瘤负荷。2)术前抽血大规模扩增免疫细胞,术中留取肿瘤组织制备DC疫苗,术后全身创伤炎症反应过后免疫低下时,亦是干细胞及大量细胞因子(IL-1/IL-6/EGF/VEGF/TGF-等,往往促进肿瘤生长)释放,进行组织修复时,尽早开始多种免疫细胞联合输注,保护和调动预存免疫功能,加强免疫监视,清除残留肿瘤细胞。3)其后对敏感的病种适当化疗,清理脉管中残留肿瘤细胞;降低抑制性免疫细胞亚群(调节型T细胞,Treg),及血中白细胞总数,腾留空间,为继续回输活化的免疫细胞,修复与重建自身抗肿瘤免疫功能打下基础。本团队总结了数百病例,分析了该疗法对于Ⅲ/Ⅳ期胃癌的疗效。观察到手术+化疗+免疫治疗组与传统手术+化疗组比较,中位生存期显著延长,一年和三年生存率均显著提高,并且患者生活质量明显改善。在结直肠癌患者,该疗法与传统治疗组相比,亦获得三年和五年生存率显著提高的疗效。

  3.在取得上述疗效的基础上,我们进一步探索了中西医整合的系统治疗模式。由于肿瘤病人体内具有毒、瘀、痰、湿等病邪积滞的邪实因素,免疫活性细胞过继转移到体内后,如体内这些病邪不驱除,整体内环境不改善,亦不能充分和持久地发挥作用,无法修复与重建自身抗肿瘤免疫功能。因此,应尽早实施中医药内治与外治,调整机体整体内环境和局部微环境;及时进行心理辅导,帮助患者及其家属正确认识肿瘤,树立战胜疾病的信心,从心理神经免疫学的角度出发,尽可能地解除心理因素对免疫系统的抑制;指导患者采取健康的生活方式及工作态度,以及健康的膳食与营养物补充,引领患者走向康复。

  本团队探索并实践的传统手段与现代生物技术相结合以及中西医整合的抗肿瘤绿色治疗模式,既遵循了中国传统医学的整体观,又发挥了西方医学与现代科技的优势,为恶性肿瘤患者所期望的减少全身性残酷治疗,改善生活质量,切实延长生存期带来了福音。
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    徐老师从一个崭新的角度诠释了免疫细胞治疗。用的方法似乎是整体论,和绝大多数老师采用的还原论的思路是截然不同的。或许整体论的思路是一条未来之路,因为肿瘤系统和免疫系统都更适合用整体论的思路来对待。感谢徐老师的创新思路和对患者高度的责任感。

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