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用源自肾细胞癌的短期细胞系的自体肿瘤细胞疫苗治疗肾癌。

Treatment of kidney cancer with autologous tumor cell vaccines of short-term cell lines derived from renal cell carcinoma.

作者信息

Dillman R O, Barth N M, VanderMolen L A, Garfield D H, De Leon C, O'Connor A A, Mahdavi K, Nayak S K

机构信息

Hoag Cancer Center, One Hoag Drive, Building 41, Newport Beach, California 92658, USA.

出版信息

Cancer Biother Radiopharm. 2001 Feb;16(1):47-54. doi: 10.1089/108497801750096023.

Abstract

BACKGROUND

We established short-term cultures of autologous tumors from patients with renal carcinoma for use as active specific immunotherapy (i.e., autologous vaccine).

METHODS

Between 9/91 and 9/99 the cell biology laboratory of the Hoag Cancer Center received 69 kidney tumor samples that had been surgically excised, including 43 primary tumors and 26 metastatic lesions. Efforts were made to establish short-term tumor cell cultures to use as autologous tumor cell vaccines. Prior to treatment, patients underwent a baseline skin test for delayed tumor hypersensitivity (DTH) and then received s.c. injections of 10 million irradiated tumor cells that were given with various adjuvants weekly x3 and then monthly x5.

RESULTS

Cell lines were established for 55/69 patients (80%) including 36/43 (84%) from primary tumors and 19/26 (73%) from distant metastases. Vaccines were prepared for 41 patients; 27 were treated. At the time of this analysis, follow up data was available for 26 patients with a median follow up > 5 years. Treatment was well-tolerated. Of 10 patients who had no evident disease at the time of treatment, nine were alive 1-8 years later; 5/8 had conversion of their DTH test from negative to positive. For 16 patients with measurable metastatic disease at the time of treatment, there were no objective tumor responses; their median survival was 5.0 months. Among these 16 patients, only 1/8 DTH tests converted, but three had a positive baseline DTH test; one was previously treated with interleukin-2 and tumor infiltrating lymphocytes and two others were previously treated with autolymphocyte therapy.

CONCLUSIONS

Vaccine therapy with short-term cultures of autologous tumor cells is feasible, well-tolerated and associated with conversion of DTH and long-term survival in patients who are free of disease at the time treatment is initiated. However, significant anti-tumor responses were not seen in patients with measurable disease at the time vaccine treatment was initiated.

摘要

背景

我们建立了来自肾癌患者的自体肿瘤短期培养物,用作主动特异性免疫疗法(即自体疫苗)。

方法

在1991年9月至1999年9月期间,霍格癌症中心的细胞生物学实验室接收了69份经手术切除的肾肿瘤样本,其中包括43份原发性肿瘤和26份转移病灶。努力建立短期肿瘤细胞培养物以用作自体肿瘤细胞疫苗。治疗前,患者接受延迟性肿瘤超敏反应(DTH)的基线皮肤试验,然后皮下注射1000万经照射的肿瘤细胞,这些细胞与各种佐剂一起每周注射3次,然后每月注射5次。

结果

为69例患者中的55例(80%)建立了细胞系,其中包括原发性肿瘤患者中的36/43例(84%)和远处转移患者中的19/26例(73%)。为41例患者制备了疫苗;27例患者接受了治疗。在本次分析时,有26例患者的随访数据,中位随访时间>5年。治疗耐受性良好。在治疗时无明显疾病的10例患者中,9例在1至8年后存活;8例中有5例的DTH试验从阴性转为阳性。对于治疗时有可测量转移疾病的16例患者,没有客观的肿瘤反应;他们的中位生存期为5.0个月。在这16例患者中,只有8例中的1例DTH试验转为阳性,但3例基线DTH试验为阳性;1例曾接受过白细胞介素-2和肿瘤浸润淋巴细胞治疗,另外2例曾接受过自体淋巴细胞治疗。

结论

用自体肿瘤细胞短期培养物进行疫苗治疗是可行的,耐受性良好,并且与治疗开始时无疾病患者的DTH转化和长期生存相关。然而,在疫苗治疗开始时患有可测量疾病的患者中未观察到显著的抗肿瘤反应。

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