共查询到20条相似文献,搜索用时 0 毫秒
1.
OBJECTIVE: Dendritic cell (DC) vaccination against cancer is a new specific immunotherapeutic approach given with either therapeutic or adjuvant intent. We provide a review of DC vaccination as a treatment for metastatic renal cell carcinoma (RCC). METHOD: A total of 197 patients with metastatic RCC were treated with DC vaccination in 14 phase I/II clinical trials. Different vaccine preparations, administration routes, and treatment schedules have been tested in these trials. Clinical response and immune response were analysed. RESULTS: Seventy-three (37%) patients had clinical response with 4 complete responses, 8 partial responses and 61 disease stabilisations, whereas 4 patients had mixed response, but most of these responses have not been transformed into durable clinical effects. Immune responses were observed in a subset of the treated patients but were not always associated with a clinical response. Only mild toxicity was observed in these trials. CONCLUSION: DC vaccination therapy in patients with metastatic RCC is currently experimental but the results are encouraging with achievement of tumour regression and induction of antigen-specific immune response combined with minimal toxicity in a subset of the treated patients. Future emphasis should be placed on therapy in the adjuvant setting because patients with minimal residual disease are more likely to benefit from the treatment. Combination approaches with DC vaccination and immune-enhancing therapies or antiangiogenic therapy should be further investigated to develop new and more efficient treatment strategies for patients with RCC. 相似文献
2.
目的 观察手术联合树突状细胞治疗肾透明细胞癌的临床效果,为肾癌治疗提供依据.方法 入组患者分为A、B两组,A组(n=33)为术后接受细胞治疗组,B组(n=37)为单纯手术治疗组.所有入组患者分别于手术治疗前8周及治疗后8周采外周血行流式细胞术检测T淋巴细胞亚群(CD3+、CD4+、CD8+、CD4 +/CD8+比值),了解治疗前后机体免疫水平.结果 Ⅰ、Ⅱ期患者A、B组治疗前后T淋巴细胞亚群差异无统计学意义(P>0.05);Ⅲ期患者A组治疗前后T淋巴细胞亚群差异有统计学意义(P<0.05),B组治疗前后T淋巴细胞亚群差异无统计学意义(P>0.05).A组治疗前后T淋巴细胞亚群差异有统计学意义(P<0.05),B组差异无统计学意义.结论 手术联合树突状细胞治疗可明显提高Ⅲ期肾透明细胞癌患者术后免疫功能,对肾癌治疗具有积极意义. 相似文献
3.
Introduction Although most vaccines target foreign infectious agents, therapeutic cancer vaccines target both well-established and metastatic
tumor cells expressing tumor antigens. Active immunotherapy is intended to enhance or activate the immunosurveillance of an
individual through a therapeutic vaccine. Renal cell carcinoma (RCC) is one of the most immunoresponsive cancers in humans,
which in turn makes it an ideal candidate for immune based therapies.
Method Several types of therapeutic vaccines have been tested and applied in the clinical setting and can be divided into cell-based
vaccines including direct application of inactivated autologous tumor cells, gene modified tumor cell-based, dendritic cell-based
(expressing RCC derived tumor antigens), and non-cell-based vaccines. This review will examine the current status of cell-based
vaccine immunotherapy and focuses on non-cell-based vaccine strategies.
Conclusion Recent advances in molecular targeting therapy have introduced a battery receptor tyrosine kinase (RTK) and mTOR inhibitors
that provide promising treatment options, however, the tolerability of tumor vaccines and the success of clinical effectiveness
in selected populations combined with recent advances in cellular therapies warrant the continued exploration of novel methods
of tumor vaccine therapies in the clinical setting. 相似文献
4.
肾癌患者治疗方法的选择 总被引:2,自引:0,他引:2
目的:探讨肾细胞癌的不同手术方式、术前肾动脉栓塞及免疫治疗的临床应用价值。方法:回顾性分析179例肾细胞癌患者的临床资料。对患者的临床资料分组进行对比,并对治疗效果和随访结果作进一步统计学分析。结果:小肾癌行肾癌根治术与保留肾组织手术效果比较,在手术时间、术后住院时间、术后5年生存率上差异均无统计学意义(P>0.05);78例术前行选择性肾动脉栓塞者,手术证实栓塞效果满意。结论:保肾单位手术是治疗局限性小肾癌的有效手段;较大的肾癌术前进行肾动脉栓塞术便于手术切除病灶,提高了肿瘤的切除率;免疫治疗是继手术治疗之后的又一种主要临床治疗方式,尤其肿瘤疫苗的出现,对于晚期肾癌及转移癌效果明显。 相似文献
5.
树突状细胞是目前已知最有效的专职抗原提呈细胞,能诱导针对肿瘤的特异性细胞毒性T淋巴细胞反应,在抗肿瘤免疫中发挥着重要作用.运用树突状细胞的这一特性制备的肿瘤疫苗在体外和体内实验都已证明其抗肿瘤效应.近年来,基因修饰的树突状细胞疫苗由于其更出色的抗肿瘤效应成为研究的热点.本文就目前基因修饰的树突状细胞疫苗的研究现状,包括... 相似文献
6.
7.
树突状细胞疫苗诱导免疫效应细胞对PC3生长的抑制作用 总被引:3,自引:9,他引:3
耳的体内外观察多种细胞因子及肿瘤相关抗原(TAA)体外培养的树突状细胞(DC)诱导免疫效应细胞对PC3的抑制。方法用淋巴细胞分离液分离抗凝新鲜全血以获得单核细胞(PBMC),用贴壁法获取DC和去DC的单核细胞(免疫效应细胞),并分别用粒/巨噬细胞集落刺激因子(GM-CSF)、人白细胞介素(IL)-4、肿瘤坏死因子(TNF)-α、PC3肿瘤相关抗原(PC3TAA)和人白介素2(IL-2)培养正常人DC和免疫效应细胞,5.6d后将DC和免疫效应细胞混合培养1-2d。观察DC,免疫效应细胞生长状况。酶法检测DC诱导免疫效应细胞对PC3的毒性作用。体内观察DC诱导免疫效应细胞和DC培养上清液对裸鼠PC3移植瘤的生长抑制作用。结果体外多种细胞因子和肿瘤相关抗原能有效引起DC增殖。DC疫苗诱导免疫效应细胞对PC3的最大杀伤效率为62.4%。体内实验见:阴性对照组Ⅰ,单纯细胞治疗组Ⅲ及其联合培养上清液治疗组Ⅳ裸鼠均于第12天发生移植瘤;预防治疗组Ⅱ,观察30d时,6例只有2例发生移植瘤;于移植瘤产生后的第45天处死所有裸鼠并称瘤体的重量,各组比较差异有统计学意义(P〈0.05),两两比较。组Ⅰ分别与组Ⅱ、Ⅲ比较差异有统计学意义(P〈0.001),组Ⅰ与组Ⅳ、组Ⅱ与组Ⅲ比较差异有统计学意义(P〈0.05)。结论DC疫苗在抗恶性肿瘤中有重要作用。 相似文献
8.
Rationale for immunotherapy of renal cell carcinoma 总被引:2,自引:0,他引:2
Summary Metastasis to distant organs is the principal cause of death from renal cell carcinoma (RCC). No commonly accepted therapy is available for disseminated RCC at present. Immunotherapy is a mode of therapy that either interferes with the immune system or makes use of drugs that have been derived from soluble mediators of the immune system. Several lines of evidence suggest that combinations of genetically engineered cytokines (e.g. interleukin-2 and interferon alpha) may be particularly active in the treatment of advanced RCC. There are two major rationales for considering immunotherapy for RCC: (1) there is currently no other therapy available, and (2) there is hardly any innovative approach besides immunotherapy. Still, immunotherapy is far from being a standard therapy for disseminated RCC. 相似文献
9.
Sarcomatoid transformation in renal cell carcinoma, so called sacromatoid RCC (sRCC), is associated with an aggressive behavior and a poor prognosis. Current therapeutic approaches are largely ineffective. Recent studies looking into the genomic and molecular characterization of sRCCs have provided insights into the biology and pathogenesis of this entity. These advances in molecular signatures may help development of effective treatment strategies. We herein present a review of recent developments in the pathology, biology, and treatment modalities in sRCC. 相似文献
10.
乳腺癌细胞抗原负载的自体树突状细胞体内诱导特异性T细胞应答 总被引:1,自引:0,他引:1
目的 以乳腺癌细胞抗原体外负载自体树突状细胞(DCs)对24例乳腺癌患者进行自身免疫,探讨其体内诱导特异性T细胞免疫应答的能力.方法 新鲜癌组织制备成热休克凋亡细胞抗原负载外周单核细胞来源DC,分别在采血后第1、2、4、6周于患者腹股沟淋巴结富集区进行皮内注射,细胞剂量为4×10+~6×106/次.结果 DC免疫治疗后患者血清抗瘤免疫因子水平明显上升:白细胞介素(IL)-2治疗前为(33.8±7.2)ng/L,治疗后为(68.5±12.4)ng/L;IL-12治疗前为(48.5±10.9)ng/L,治疗后为(118.2±31.5)ng/L;肿瘤坏死因子(TNF)-α治疗前为(18.7±5.3)ng/L,治疗后为(78.3±11.5)ng/L;干扰素(IFN)-γ治疗前为(20.5±6.3)ng/L,治疗后为(92.6±14.9)ng/L,治疗前后比较差异有统计学意义(P<0.01);DTH试验阳性率为7/10;4/10例IFN-γ+CD8+T细胞频率较治疗前明显增加.随访发现:除1例患者在治疗后3个月内疾病进展(PD),其余患者病情稳定无复发与转移症状(SD).结论 以乳腺癌细胞为抗原负载自体DC免疫患者,能够有效提高患者非特异免疫水平,激发体内特异性T细胞免疫应答,是一种安全、副反应较小、有效的乳腺癌辅助治疗手段. 相似文献
11.
目的 观察自体负载肿瘤抗原树突状细胞(DC)对大鼠甲状腺癌的治疗作用.方法 建立Wistar荷瘤大鼠动物模型,随机分为治疗组和对照组,治疗组静脉输入负载肿瘤抗原DC、对照组输入生理盐水,检测分析2组血清中自细胞介素(IL)-12、IL-8表达水平,以及瘤重、瘤体体积及大鼠存活.结果 治疗组与对照组瘤重、瘤体体积、存活期、IL-12及IL-8表达水平分别为:(3.56±0.79)g比(4.97±0.56)g、(3.98±0.84)cm3比(5.06±0.58)cm3、(36.0±3.0)d比(28.0±3.2)d、(368.9±21.7)ng/L比(227.7±13.4)ng/L和(218.9±19.3)ng/L比(371.2±24.1)ng/L(P值分别<0.01、<0.01、<0.05、<0.01、<0.01).结论 自体负载肿瘤抗原DC对甲状腺癌具有较好的抑瘤效应,可延长荷瘤鼠的生存期. 相似文献
12.
目的以肿瘤细胞与树突状细胞(dendriticcells,DCs)相融合使融合细胞能将肿瘤抗原递呈给T细胞,并提供T细胞激活所必需的第二信号,借此激活机体的抗肿瘤免疫。方法通过PEG法将鼠源性胃癌细胞MFC与小鼠DC进行融合(T/DC),融合后经50Gy电子线照射,以1×106肿瘤疫苗于小鼠皮下注射免疫2次,间隔1周后接种,后一次免疫后1周于小鼠皮下接种5×105MFC胃癌细胞。肿瘤细胞接种3周后处死实验动物,测量肿瘤大小、外周血NK活性和脾细胞CTL活性。结果肿瘤接种后一周对照组小鼠皮下均有肿瘤生长,而T/DC免疫组均无皮下可触及的肿瘤(10/10),10天后T/DC免疫组才有4/10只鼠皮下出现可触及的肿瘤,3周后对照组肿瘤体积明显大于T/DC免疫组。经T/DC免疫后小鼠生存期明显较对照组延长,对照组于肿瘤接种后2周开始有小鼠衰竭死亡,至肿瘤接种后3周对照组仅有3只存活,T/DC免疫组有8只鼠存活,并仍有3只无肿瘤生长。经T/DC免疫后,小鼠NK活性和肿瘤特异性CTL活性均明显提高,T/DC免疫组和对照组MFC特异性CTL活性分别为30.09%和7.12%。结论肿瘤细胞鄄DC融合的肿瘤疫苗可通过加强抗原递呈激活肿瘤特异性CTL而具明显的抗肿瘤活性。 相似文献
13.
14.
Immunotherapy has recently catapulted to the forefront of treatments for patients with solid tumors. Given its inherent immunogenic properties, renal cell carcinoma (RCC) has historically responded to immunotherapy and remains primed for further development. Although immunotherapy with high-dose interleukin 2 was a primary treatment for advanced RCC (aRCC), recent discoveries of key molecular and immunological alterations have led to the FDA-approval of nivolumab, an antiprogrammed cell death inhibitor, which has demonstrated an overall survival in patients with previously treated aRCC. However, despite recent therapeutic advances, aRCC remains an incurable disease for most patients. In this review, we assess the current landscape and future developments of immunotherapy in aRCC. 相似文献
15.
PURPOSE: Renal cell carcinoma (RCC) is known for its immunological susceptibility. Unfortunately RCC lacks specific tumor antigens for the induction of specific immunotherapy. We investigated the role of telomerase as a tumor antigen and pulsed dendritic cells (DCs) as antigen presenting cells with an immunogenic peptide from telomerase. MATERIAL AND METHODS: DCs and immunological effector cells, that is cytokine induced killer (CIK) cells, from patients with RCC or healthy donors were generated. CIK cells were co-cultured with telomerase peptide pulsed DCs. CIK cells were tested for cytotoxic activity against primary cultures. Using the dimer technique we determined the percent of telomerase specific T cells. Activation status was identified using interferon-gamma secretion assay. RESULTS: After pulsing DCs with telomerase peptide co-cultured CIK cells had a significant increase in cytotoxic activity against tumor cells compared with CIK cells without co-culture, that is 100% at an effector-to-target ratio of 60:1 vs 41.7% (p <0.05). Using a complete autologous model with immunological cells derived from patients with metastatic RCC we were able to induce cytotoxicity against autologous, telomerase positive primary cell cultures. We could detect 2.4% telomerase specific effector cells after co-culture with peptide pulsed DCs, which secreted interferon-gamma after re-stimulation. CONCLUSIONS: Telomerase could serve as a specific tumor associated antigen for RCC. The presentation of telomerase peptide by DCs to lymphocytes allows the generation of antigen specific cytotoxic effector cells. 相似文献
16.
Alp Tuna Beksac David J. Paulucci Kyle A. Blum Shalini Singh Yadav John P. Sfakianos Ketan K. Badani 《Urologic oncology》2017,35(8):507-515
Introduction
In recent years, molecular characterization of renal cell carcinoma has facilitated the identification of driver genes, specific molecular pathways, and characterization of the tumor microenvironment, which has led to a better understanding of the disease. This comprehension has revolutionized the treatment for patients with metastatic disease, but despite these advancements many patients will develop resistance leading to treatment failure. A primary cause of this resistance and subsequent treatment failure is tumor heterogeneity. We reviewed the literature on the mechanisms of tumor heterogeneity and its clinical implications.Methods
A comprehensive literature search was performed using the MEDLINE/PubMed Index.Results
Intertumor and intratumor heterogeneity is possibly a reason for treatment failure and development of resistance. Specifically, the genetic profile of a renal tumor differs spatially within a tumor as well as among patients. Genomic mutations can change temporally with resistant subclones becoming dominant over time.Conclusions
Accounting for intratumor and intertumor heterogeneity with better sampling of cancer tissue is needed. This will hopefully lead to improved identification of driver mutations and actionable targets. Only then, we can move past the one-size-fits-all approach toward personalized treatment based on each individual?s molecular profile. 相似文献17.
目的:研究人卵巢癌细胞光动力学细胞裂解物对体外免疫应答反应的影响.方法:体外诱导培养人脐血树突状细胞(DC).人卵巢癌细胞SKOV3分别用光动力学方法(激光照射)及冻融的方法制备细胞裂解物,与DC共培养48 h,RPMI1640与DC培养作为阴性对照,采用流式细胞仪检测DC免疫表型CD1a、CD80、CD86、HLA-... 相似文献
18.
Marcin Matuszewski Ph.D. Jerzy Michaj?owski M.D. Igor Michaj?owski M.D. Katarzyna Ruckermann-Dizurdzińska Ph.D. Jacek M. Witkowski Ph.D. Wojciech Biernat Ph.D. Kazimierz Krajka Ph.D. 《Urologic oncology》2011,29(6):724
Purpose
With the development of diagnostic techniques, renal cell carcinoma (RCC) is currently diagnosed in earlier stages, allowing the introduction of less invasive techniques in its management. One of the most promising new treatment methods is based on the utilization of high temperature created by radiofrequency current circulating around the needle probe introduced into the tumor. Besides the direct destruction of the cancer tissue, the treatment may induce immunologic reaction to tumor antigens released from destroyed tumor cell. This paper describes changes observed in the peripheral blood lymphocyte population after radiofrequency ablation (RFA) of RCC.Methods
Blood was tested before, and 2, 4, and 6 weeks after the RFA in 6 patients with RCC for the proportions and numbers of CD3+, CD3+HLA-DR+, CD3+CD4+, CD3+CD8+, and CD56+CD16+ cells. The blood was stained with fluorochrome-conjugated monoclonal antibodies and percentages of cells expressing various markers were determined by flow cytometry.Results
In all patients, the changes were most pronounced 2 weeks after the procedure. The proportion of CD4+ and CD8+ lymphocytes were changed. In 1 patient, an increase in both CD4+ and CD8+ cells was observed. In 5 out of 6 patients, the proportion of activated (DR+) cells was increased over the whole follow-up period with the highest values in the second week after RFA. The percentage of the CD56+CD16+ was decreased in most of the patients.Conclusions
Our study confirms that in the majority of patients, RFA of the renal tumors causes significant changes in the proportion of the peripheral immune cells. We suggest that the results presented in this article shows the necessity for further studies. 相似文献19.
De-Hong Cao Liang-Ren Liu Yu Fang Ping Tang Tao Li YunJin Bai Jia Wang Qiang Wei 《Urologic oncology》2017,35(11):661.e15-661.e21
Objective
To evaluate the clinical efficacy and safety of simple tumor enucleation (TE) for clinical T1 renal cell carcinoma.Materials and methods
A systematic search of PubMed, EMBASE, and Cochrane Central Register of Controlled Trials databases was performed to identify all trials that compared TE and traditional partial nephrectomy (PN) for patients with clinical T1 renal cell carcinoma.Results
A total of 7 studies involving 3,218 patients were identified and included in this meta-analysis. Compared with the PN group, the TE group had significantly shorter estimated operation times (mean difference [MD] = ?21.93; 95% CI: ?31.07 to ?12.78; P< 0.001), shorter warm ischemia times (MD = ?1.96; 95% CI: ?3.80 to ?0.13; P = 0.04), less blood loss (MD = ?36.63; 95% CI: ?57.49 to ?15.77; P = 0.0006), and lower surgical complication rates (odds ratio [OR] = 0.66; 95% CI: 0.47–0.92; P = 0.02). Furthermore, there was no significant difference between the 2 groups in hospital stay duration (MD = ?0.46; 95% CI: ?0.93 to 0.02; P = 0.06), changes in estimated glomerular filtration rate (MD = 3.35; 95% CI: ?2.78 to 9.48; P = 0.28), positive surgical margin rates (OR = 0.34; 95% CI: 0.10–1.14; P = 0.08), and local recurrence rates (OR = 0.71; 95% CI: 0.24–2.06; P = 0.52).Conclusion
Compared to traditional PN, TE is an effective and safe treatment for T1 renal tumors, and TE appears to have acceptable early oncology outcomes. Owing to the limited number of clinical trials and the predominantly retrospective data on this subject, there is a need for properly designed studies to confirm our findings. 相似文献20.
Qun Lu Changwei Ji Xiaozhi Zhao Yao Fu Suhan Guo Guangxiang Liu Shiwei Zhang Xiaogong Li Weidong Gan Hongqian Guo 《Urologic oncology》2017,35(10):603.e15-603.e20