Clinical Responses in a Phase II Study Using Adoptive Transfer of Short-term Cultured Tumor Infiltration Lymphocytes in Metastatic Melanoma Patients
Clinical Responses in a Phase II Study Using Adoptive Transfer of Short-term Cultured Tumor Infiltration Lymphocytes in Metastatic Melanoma Patients
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DOI：
10.1158/1078-0432.ccr-10-0041
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发表时间：
2010-05-01
影响因子：
11.5
通讯作者：
Schachter, Jacob
中科院分区：
文献类型：
--
作者：
Besser, Michal J.;Shapira-Frommer, Ronnie;Schachter, Jacob
目的：自体肿瘤浸润淋巴细胞（TIL）过继性细胞疗法在转移性黑色素瘤患者中已显示出有前景的结果。尽管已报道客观缓解率超过50%，但这种方法的缺点是TIL生产劳动强度大以及入组患者的退出率非常高，限制了其广泛应用。先前的研究表明，TIL培养周期短与临床反应之间存在明显的相关性。因此，我们使用了一种新的TIL生产技术，即使用未筛选、最低限度培养的大量TIL（年轻TIL）。年轻TIL的使用不限于人类白细胞抗原（HLA）-A2患者。本研究的目的是探讨在白细胞清除性化疗后过继性输注年轻TIL在对白细胞介素 - 2和化疗耐药的转移性黑色素瘤患者中的疗效和毒性。
实验设计：90%的患者成功培养出年轻TIL，使得大多数入组患者能够接受治疗。我们在此报告20例评估患者的结果。
结果：根据实体瘤反应评估标准，50%的患者达到了客观临床缓解，包括2例持续完全缓解（20 +、4 +个月）和8例部分缓解（无进展生存期：18 +、13 +、10 +、9、6 +、4、3 +和3个月）。所有缓解者目前均存活。另外4例患者病情稳定。副作用是短暂的且可控制。
结论：我们表明，白细胞清除性化疗后输注短期培养的TIL可使50%的转移性黑色素瘤患者肿瘤消退，且毒性可控制。令人信服的临床结果以及流程的简化可能因此对癌症的细胞疗法产生重大影响。《临床癌症研究》；16(9)；2646 - 55。（C）2010美国癌症研究协会。
Purpose: Adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TIL) has shown promising results in metastatic melanoma patients. Although objective response rates of over 50% have been reported, disadvantages of this approach are the labor-intensive TIL production and a very high drop-out rate of enrolled patients, limiting its widespread applicability. Previous studies showed a clear correlation between short TIL culture periods and clinical response. Therefore, we used a new TIL production technique using unselected, minimally cultured, bulk TIL (Young-TIL). The use of Young-TIL is not restricted to human leukocyte antigen (HLA)-A2 patients. The purpose of this study is to explore the efficacy and toxicity of adoptively transferred Young-TIL following lympho-depleting chemotherapy in metastatic melanoma patients, refractory to interleukin-2 and chemotherapy.Experimental Design: Young-TIL cultures for 90% of the patients were successfully generated, enabling the treatment of most enrolled patients. We report here the results of 20 evaluated patients.Results: Fifty percent of the patients achieved an objective clinical response according to the Response Evaluation Criteria in Solid Tumors, including two ongoing complete remissions (20+, 4+ months) and eight partial responses (progression-free survival: 18+, 13+, 10+, 9, 6+, 4, 3+, and 3 months). All responders are currently alive. Four additional patients showed disease stabilization. Side effects were transient and manageable.Conclusion: We showed that lympho-depleting chemotherapy followed by transfer of short-term cultured TIL can mediate tumor regression in 50% of metastatic melanoma with manageable toxicity. The convincing clinical results combined with the simplification of the process may thus have a major effect on cell therapy of cancer. Clin Cancer Res; 16(9); 2646-55. (C) 2010 AACR.