Efficient and reproducible generation of tumour-infiltrating lymphocytes for renal cell carcinoma.
Efficient and reproducible generation of tumour-infiltrating lymphocytes for renal cell carcinoma.
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DOI：
10.1038/bjc.2015.96
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发表时间：
2015-04-28
影响因子：
8.8
通讯作者：
Gilham, D. E.
中科院分区：
文献类型：
--
作者：
Baldan, V.;Griffiths, R.;Hawkins, R. E.;Gilham, D. E.
肿瘤浸润淋巴细胞（TIL）疗法在晚期恶性黑色素瘤患者的治疗中显示出巨大的前景。然而，将TIL疗法转化为非黑色素瘤肿瘤如肾细胞癌不太成功，主要限制是不能从原发性和转移性肿瘤组织可重复地产生TIL。对原发性和转移性肾细胞癌活组织检查进行差异性肿瘤解聚方法和程序，其刺激所测试的TIL的特异性扩增，以确定哪些可靠产生的TIL保持抗肿瘤特异性。酶解或酶解/机械解的组合导致从肾细胞癌活检组织中释放出相等数量的TIL。用抗CD 3/抗CD 28包被的顺磁珠激活分离的TIL后，在90%的起始培养物中实现了成功的TIL扩增。当使用GentleMACS酶/机械系统分解肿瘤时，自体肿瘤的T细胞识别频率增强。TIL可以从肾细胞癌活检组织中一致地产生，在体外扩增后保持自体肿瘤识别。虽然解聚的方法对TIL生长的成功几乎没有影响，但是保留细胞表面结构的方法促进自体肿瘤的TIL识别，这在表征扩增的TIL群体的功能性方面是重要的。
Tumour-infiltrating lymphocyte (TIL) therapy is showing great promise in the treatment of patients with advanced malignant melanoma. However, the translation of TIL therapy to non-melanoma tumours such as renal cell carcinoma has been less successful with a major constraint being the inability to reproducibly generate TILs from primary and metastatic tumour tissue. Primary and metastatic renal cell carcinoma biopsies were subjected to differential tumour disaggregation methods and procedures that stimulate the specific expansion of TILs tested to determine which reliably generated TIL maintained antitumour specificity. Enzymatic or combined enzymatic/mechanical disaggregation resulted in equivalent numbers of TILs being liberated from renal cell carcinoma biopsies. Following mitogenic activation of the isolated TILs with anti-CD3/anti-CD28-coated paramagnetic beads, successful TIL expansion was achieved in 90% of initiated cultures. The frequency of T-cell recognition of autologous tumours was enhanced when tumours were disaggregated using the GentleMACS enzymatic/mechanical system. TILs can be consistently produced from renal cell carcinoma biopsies maintaining autologous tumour recognition after expansion in vitro. While the method of disaggregation has little impact on the success of TIL growth, methods that preserve the cell surface architecture facilitate TIL recognition of an autologous tumour, which is important in terms of characterising the functionality of the expanded TIL population.
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DOI：
10.1038/nrc3322
发表时间：
2012-10
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Gattinoni L;Klebanoff CA;Restifo NP
通讯作者：
Restifo NP
影响因子：
3.9
作者：
Dudley, ME;Wunderlich, JR;Rosenberg, SA
通讯作者：
Rosenberg, SA
影响因子：
11.5
作者：
Besser, Michal J.;Shapira-Frommer, Ronnie;Schachter, Jacob
通讯作者：
Schachter, Jacob
DOI：
10.1158/1078-0432.ccr-10-1297
发表时间：
2010-12-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Dudley ME;Gross CA;Langhan MM;Garcia MR;Sherry RM;Yang JC;Phan GQ;Kammula US;Hughes MS;Citrin DE;Restifo NP;Wunderlich JR;Prieto PA;Hong JJ;Langan RC;Zlott DA;Morton KE;White DE;Laurencot CM;Rosenberg SA
通讯作者：
Rosenberg SA
影响因子：
5.5
作者：
Takeuchi, Makoto;Inoue, Toshiya;Kibata, Masayoshi
通讯作者：
Kibata, Masayoshi