Dedeepiya V, Terunuma H, Manjunath S, Senthilkumar R, Thamaraikannan P, Srinivasan T, HelenReena C, Preethy S, Abraham S
Nichi-In Centre for Regenerative Medicine , Chennai, India.
Biotherapy Institute of Japan , Tokyo, Japan.
J Stem Cells Regen Med. 2011 Oct 30;7(2):95. eCollection 2011.
Autologous Natural Killer (NK) cells and Cytotoxic T Lymphocytes (CTLs) based immune-cell therapy, otherwise called as Autologous Immune enhancement therapy (AIET), though has been in clinical practice in several developed nations since early 90s, in India it is in infancy due to lack of technological knowhow. Our institute has been providing the AIET cell expansion services since 2005 and we here in report our experience in 30 such patients of both solid tumours and hematological malignancies.
MATERIALS & METHODS: The number of AIET transfusions in each patient ranged from one to six. All the patients included had Stage III to IV malignancy. AIET was either given along with the chemotherapy or after the completion of a minimum of six cycles of chemotherapy in all the patients. 70 ml of Peripheral Blood was collected each time. The protocol followed was as per Terunuma et al (Breast Cancer 2010) which uses only the patients' autologous plasma for expansion of the Natural Killer Cells and Cytotoxic T lymphocytes from the peripheral blood. The cells were cultured for a period of 10 to 16 days and then transfused to the patients intravenously. The cells were subjected to Flow cytometry before and after the in vitro expansion. Feeder layers were not used in the procedure of in vitro expansion at any stage.
The percentage of NK cells and CTLs after expansion by flow cytometry ranged from 60 to 82 %. There were no adverse reactions in any of the patients following transfusion. The mean prolonged survival time was 15 months and 27% of the patients had Static non-progressive disease after the therapy. Two patients reported significant decrease in Cancer marker levels after AIET and among the terminally ill, two had more than two years survival. All the patients reported improvement in quality of life and resumption of appetite following AIET.
Optimal in vitro expansion of NK cells and CTLs of patients with stage III-IV cancer either concurrently or after chemotherapy could be accomplished using autologous serum without use of feeder layers. The In vitro expanded NK cells and CTLs when given intravenously decrease the tumor size and prolong the survival without any adverse effect in our experience.
基于自体自然杀伤（NK）细胞和细胞毒性T淋巴细胞（CTL）的免疫细胞疗法，即自体免疫增强疗法（AIET），尽管自90年代初以来已在多个发达国家应用于临床实践，但在印度由于缺乏技术知识仍处于起步阶段。自2005年以来，我们研究所一直在提供AIET细胞扩增服务，在此我们报告30例实体瘤和血液系统恶性肿瘤患者的治疗经验。
每位患者接受AIET输血的次数为1至6次。所有纳入患者均为III期至IV期恶性肿瘤。在所有患者中，AIET要么与化疗同时进行，要么在至少六个周期的化疗完成后进行。每次采集70毫升外周血。遵循的方案依据Terunuma等人（《乳腺癌》2010年）的方法，该方法仅使用患者自身血浆从外周血中扩增自然杀伤细胞和细胞毒性T淋巴细胞。细胞培养10至16天，然后静脉输注给患者。在体外扩增前后对细胞进行流式细胞术检测。在体外扩增过程的任何阶段均未使用饲养层。
通过流式细胞术检测，扩增后NK细胞和CTL的百分比范围为60%至82%。输血后所有患者均未出现不良反应。平均延长生存期为15个月，27%的患者在治疗后病情稳定无进展。两名患者在接受AIET后癌症标志物水平显著下降，在晚期患者中，两名患者存活超过两年。所有患者均报告在接受AIET后生活质量有所改善且食欲恢复。
使用自体血清且不使用饲养层，可在体外实现III - IV期癌症患者NK细胞和CTL的最佳扩增，无论是在化疗期间还是化疗后。根据我们的经验，静脉输注体外扩增的NK细胞和CTL可减小肿瘤大小并延长生存期，且无任何不良反应。
