Treatment of metastatic renal cell carcinoma with nephrectomy, interleukin-2 and cytokine-primed or CD8(+) selected tumor infiltrating lymphocytes from primary tumor
Treatment of metastatic renal cell carcinoma with nephrectomy, interleukin-2 and cytokine-primed or CD8(+) selected tumor infiltrating lymphocytes from primary tumor
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DOI：
10.1016/s0022-5347(01)64304-0
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发表时间：
1997-09-01
影响因子：
6.6
通讯作者：
Belldegrun, A
中科院分区：
文献类型：
--
作者：
Figlin, RA;Pierce, WC;Belldegrun, A
目的：转移性肾细胞癌是一种平均生存期为6 ~ 10个月的疾病。白细胞介素-2（IL-2）是唯一获批的转移性肾细胞癌治疗方法，在一些高体力状态患者中，其缓解率为14%，且缓解持续时间较长。我们进行了一系列的IL-2加肿瘤浸润淋巴细胞治疗的试验，并报告了62例患者参加这些trials.Materials and Methods的临床结果：患者有资格，如果他们有转移性肾细胞癌与原发肿瘤的地方和东部肿瘤协作组的性能状态为0或1。患者在肾切除术前用细胞因子治疗，并制备细胞因子致敏的肿瘤浸润淋巴细胞或分离CD 8（+）肿瘤浸润淋巴细胞以输注到患者体内。62例患者中55例接受肿瘤浸润淋巴细胞联合IL-2治疗，观察其毒副反应及生存情况。7例（11%）患者无法接受全身治疗。未观察到与细胞输注相关的意外IL-2相关毒性或显著毒性。总体而言，5例患者（9.1%）达到完全缓解，14例（25.5%）达到部分缓解。这些反应是持久的，中位持续时间为14个月（范围为0.8+至64+）。从肾切除术后1年的精算生存率为65%，2年为43%，所有患者的总中位生存期为22个月（范围2至70+）。中位生存率为响应患者尚未达到（范围2至63+）。结论：这些结果表明，免疫治疗与根治性肾切除术，肿瘤浸润淋巴细胞，和IL-2提供了大量的临床受益，在大多数患者。使用富集的细胞组分的成分细胞疗法允许给予更标准化的细胞产品。目前肾切除术、肿瘤浸润淋巴细胞和IL-2的结果令人鼓舞，目前正在进行一项肾切除术、CD 8（+）肿瘤浸润淋巴细胞加IL-2与肾切除术和IL-2单独治疗的随机临床试验。
Purpose: Metastatic renal cell carcinoma is a disease with a mean survival of 6 to 10 months. Interleukin-2 (IL-2), the only approved therapy for metastatic renal cell carcinoma, is associated with a 14% response rate and durable remissions in some patients with high performance status. We performed a series of trials of IL-2 plus tumor infiltrating lymphocyte cell therapy and report the clinical results from 62 patients enrolled in these trials.Materials and Methods: Patients were eligible if they had metastatic renal cell carcinoma with the primary tumor in place and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were treated with cytokines before nephrectomy and preparation of cytokine primed tumor infiltrating lymphocytes or CD8(+) tumor infiltrating lymphocytes were isolated for infusion into patients. Of 62 patients enrolled 55 were treated with tumor infiltrating lymphocytes and IL-2, and were evaluable for toxicity, response and survival.Results: There were no postoperative mortalities. Of the patients 7 (11%) could not undergo systemic therapy. No unexpected IL-2 related toxicities or significant toxicities related to cell infusion were noted. Overall 5 patients (9.1%) achieved a complete response and 14 (25.5%) achieved a partial response. The responses were durable with a median duration of 14 months (range 0.8+ to 64+). The actuarial survival was 65% at 1 year and 43% at 2 years from the time of nephrectomy, with an overall median survival for all patients of 22 months (range 2 to 70+). The median survival for the responding patients has not yet been reached (range 2 to 63+).Conclusions: These results demonstrate that immunotherapy with radical nephrectomy, tumor infiltrating lymphocytes, and IL-2 provides substantial clinical benefit in the majority of patients. Component cellular therapy with enriched cell fractions allows the administration of a more standardized cell product. The present results with nephrectomy, tumor infiltrating lymphocytes and IL-2 are encouraging, and a randomized clinical trial of nephrectomy, CD8(+) tumor infiltrating lymphocytes, plus IL-2 versus nephrectomy and IL-2 alone is currently in progress.