负载自体肿瘤细胞裂解物的DC疫苗联合CIK治疗晚期肾癌的临床观察——附10例报告

Efficacy of Autologous Renal Tumor Cell Lysate-loaded Dendritic Cell Vaccine in Combination with Cytokine-induced Killer Cells on Advanced Renal Cell Carcinoma-a Report of Ten Cases

背景与目的:肾癌的主要治疗手段是手术,但晚期肾癌术后复发率高,加上肾癌对化疗和放疗不敏感,因此,晚期肾癌预后不佳,需要寻找新的更有效的治疗方法。本研究通过负载自体肿瘤细胞裂解物的树突细胞(dendriticcells,DC)疫苗联合细胞因子诱导的杀伤细胞(cytokine-inducedkillercells,CIK)治疗10例晚期肾癌,观察近期的临床疗效,免疫学反应及副作用。方法:分离患者外周血单核细胞,体外经GM-CSF和IL-4诱导产生DC细胞,并负载自体肿瘤细胞裂解物;T淋巴细胞经IFN-γ、IL-2、CD3单抗、IL-1α体外诱导产生CIK细胞。所有患者在切除原发病灶后,接受每周一次的皮内DC疫苗注射治疗,至少8次治疗;CIK细胞过继细胞免疫治疗,每2周一次,至少接受4次治疗。临床疗效和免疫学反应分别通过影象学检查,外周血T淋巴细胞亚群改变和迟发性超敏(delayed-typehypersensitivity,DTH)反应进行评估。结果:(1)4例有可评价病灶的患者中1例部分缓解(PR),2例疾病稳定(SD),1例进展(PD);6例没有可评价病灶的患者中1例PD,1例失访,另外4例未见疾病进展。随访时间6～20个月(中位时间11个月)。(2)与治疗前比较,治疗2个月后患者CD3+、CD4+、CD4+/CD8+、CD56+明显升高(P<0.05)。(3)包括PR患者在内的6例患者DTH反应呈现阳性。(4)除一过性的发热、畏寒外没有其它不良反应出现。结论:负载自体肿瘤细胞裂解物的DC疫苗联合CIK细胞治疗晚期肾癌有一定的近期临床疗效,能诱导出特异的抗肾癌免疫反应,并且有良好的耐受性。

BACKGROUND ＆ OBJECTIVE： Nowadays, operation is the main treatment for renal cell carcinoma （RCC）. But the prognosis of advanced RCC is poor because of its high recurrence rate and resistance to conventional treatments, such as chemotherapy and radiotherapy. Hence, novel and more effective therapeutic options for advanced RCC are needed. This study was to evaluate the clinical efficacy of autologous renal tumor lysate-loaded dendritic cells （DCs） in combination with cytokine-induced killer （CIK） cells on advanced RCC. METHODS. Peripheral blood mononuclear cells were isolated from 10 patients with advanced RCC, and cultured with granulocyte-macrophage colony-stimulating factor （GM-CSF） and interleukin-4 （IL-4） to produce DCs. The DCs were pulsed with autologous renal tumor cell lysate. T lymphocytes were cultured with interferon-γ （IFN-γ）, IL-2, CD3-moAb, and IL-1α to prepare CIKs. After nephrectomy, the patients received intradermal DC vaccination weekly for at least 8 times, and CIKs administration biweekly for at least 4 times. Clinical and immunologic responses were evaluated by imaging examination, T lymphocytes subset changes, and delayed-type hypersensitivity （DHT） reaction, respectively. RESULTS： During follow-up of 6-20 months （median, 11 months）, 1 case of partial remission （PR）, 2 cases of stable disease （SD）, and 1 case of progressive disease （PD） were identified in the 4 patients with measurable diseases; 1 case of PD was identified in the 6 patients with no measurable diseases, 1 case was lost, and no progressive disease was identified. When treated for 2 months, the levels of CD3^＋, CD4^＋, CD4^＋/CD8^＋, CD56^＋ were increased significantly （P〈0.05） as compared with those before treatment, DTH reaction was positive in 6 patients, including the patient with PR, Except transient fever and chill, no remarkable adverse event happened during or after the treatment. CONCLUSION- Autologous tumor cell lysate-pulsed DCs in combination with CIKs shows short-term efficacy on advanced RCC through inducing specific antitumor immunity, and the adverse events are tolerable.