树突状细胞瘤苗抗肿瘤临床应用进展

树突状细胞（DC）是目前功能最强的抗原提呈细胞，在机体抗肿瘤免疫中发挥重要作用。近年来，DC瘤苗抗肿瘤临床应用取得较大进展，现对DC瘤苗的制备及其在肿瘤免疫治疗中的临床应用以及存在问题作一综述。     

胃癌细胞-树突状细胞融合疫苗抗肿瘤效应的实验研究

[目的]研究胃癌细胞-树突状细胞(DC)融合疫苗对严重联合免疫缺陷(SCID)小鼠胃癌模型的抗肿瘤效应.[方法]聚乙二醇法诱导胃癌细胞BGC-823与成熟DC融合制备疫苗,将SCID小鼠胃癌模型随机均分为4组:BGC-823/DC融合疫苗组、BGC-823+DC联合组、DC组和PBS组,分别皮下注射相应疫苗、细胞或试剂,检测小鼠脾脏细胞毒性T淋巴细胞(CTL)活性、皮下移植瘤体积、核因子-κB(NF-κB)、基质金属蛋白酶-9(MMP-9)表达和癌细胞侵袭能力即穿膜细胞数.[结果]CTL活性在融合疫苗组、联合组、DC组及PBS组分别为(39.40±3.38)％、(18.07±1.49)％、(14.07±1.32)％、(10.70±1.11)％;移植瘤体积在以上四组分别为(165.03±30.96)mm3、(767.65±118.81)mm3、(1025.16±80.90)mm3、(1314.99士74.03)mm3:NF-κB表达分别为20.0％、70.0％、90.0％、100.0％;MMP-9表达分别为50.0％、80.0％、90.0％、90.0％;穿膜细胞数分别为15.17±4.67,39.73±6.09、59.36±13.87、90.86±4.97.融合疫苗组各检测指标与其他组比较均有显著差异(P＜0.05).[结论]融合疫苗能有效诱导CTL活化、下调NF-κB、MMP-9表达及癌细胞侵袭能力,产生特异性抗肿瘤免疫.     

树突状细胞与肝癌细胞瘤苗的实验研究

目的 :探讨杂交瘤苗H2 2 DC的生物学特性及特异性CTL活性。方法 :利用Metrizamide等分离小鼠脾DC ,融合DC与H2 2 细胞 ,磁式细胞分选器分选出H2 2 DC ,从BALB/C小鼠皮下接种H2 2 DC法检测小鼠脾CTL活性。结果 :(1)H2 2 DC虽在体外能分裂增殖 ,但明显低于H2 2 细胞 ,无体内致瘤性 ;(2 )活H2 2 DC免疫的小鼠 ,其脾CTL杀伤H2 2 细胞的活性明显高于对照组 (H2 2 +DC、H2 2 、PBS)小鼠 (P <0 0 1)。结论 :DC H2 2 能诱导出特异性的CTL活性 ,可望成为肝癌免疫治疗的新途径     

树突状细胞肿瘤疫苗的研究及实践进展

癌症是威胁全球人民健康的头号杀手之一,传统治疗手段(如手术、放疗、化疗)虽有进展,但癌症患者的预后仍不令人满意。发展新治疗策略仍迫在眉睫。由于树突状细胞疫苗为基础的免疫治疗能活化机体免疫细胞,通过识别肿瘤相关抗原特异性杀灭肿瘤细胞,而不伤及正常细胞,目前已经成为肿瘤治疗的一个热点。     

树突状细胞抗肿瘤实验研究进展及临床应用

树突状细胞 (dendriticcell,DC)是体内最强的抗原提呈细胞[1] ,免疫反应的产生首先是由抗原提呈细胞 (APC)捕获抗原 ,经其加工处理后将抗原信号传递给T ,B淋巴细胞 ,从而引发一系列的免疫应答。因此 ,APC是机体免疫反应的首要环节 ,能否进行有效的抗原提呈直接关系到免疫激活和免疫耐受的诱导 ,树突状细胞的最大特点是能够显著激活初始T淋巴细胞 ,诱导免疫应答。在肿瘤免疫过程中 ,T细胞介导的免疫应答起着主导作用。T细胞的致敏、激活、扩增依赖抗原提呈细胞 ,T细胞识别的肿瘤抗原不是被肿瘤细胞提呈而是被APC提呈 ,而树突状细胞是体内最具免疫治疗活力的抗原提呈细胞。因而 ,它在肿瘤免疫中的作用越来越被重视。其抗肿瘤作用目前主要在实验研究及临床Ⅰ ,Ⅱ期应用中。本文主要对树突状细胞抗肿瘤实验研究及临床应用作一综述。     

树突状细胞抗肿瘤实验研究进展及临床应用

树突状细胞(dendritic cell，DC)是体内最强的抗原提呈细胞，免疫反应的产生首先是由抗原提呈细胞(APC)捕获抗原，经其加工处理后将抗原信号传递给T，B淋巴细胞，从而引发一系列的免疫应答。因此，APC是机体免疫反应的首要环节，能否进行有效的抗原提呈直接关系到免疫激活和免疫耐受的诱导，树突状细胞的最大特点是能够显著激活初始T淋巴细胞，诱导免疫应答。在肿瘤免疫过程中，T细胞介导的免疫应答起着主导作用。T细胞的致敏、激活、扩增依赖抗原提呈细胞，T细胞识别的肿瘤抗原不是被肿瘤细胞提呈而是被APC提呈，而树突状细胞是体内最具免疫治疗活力的抗原提呈细胞。因而，它在肿瘤免疫中的作用越来越被重视。其抗肿瘤作用目前主要在实验研究及临床I，Ⅱ期应用中。本文主要对树突状细胞抗肿瘤实验研究及临床应用作一综述。     

树突状细胞疫苗治疗晚期恶性肿瘤17例的护理

树突状细胞（DC）注射是近年新兴的一种生物治疗恶性肿瘤的方法,已越来越多的被应用于临床晚期肿瘤患者。树突状细胞（clendritic cell DC）是体内功能最强的抗原提呈细胞（antigen presenting cells,APC）,成熟的DC是惟一能激活幼稚T淋巴细胞（naive T cell）的专职抗原提呈细胞,在诱导高效而特异的抗肿瘤细胞免疫中起关键作用。     

高强度聚焦超声制备树突状细胞瘤苗对BALB/c小鼠肿瘤主动免疫的实验研究

目的探讨采用高强度聚焦超声(HIFU)制备肿瘤抗原致敏树突状细胞(DC)对正常BALB/c小鼠肿瘤的主动免疫作用。方法采用功率1000W/cm2的HIFU辐照CT-26结肠癌细胞30s,获取肿瘤抗原,与体外培养扩增第5天的DC共孵育,制备DC瘤苗。HIFU辐照法制备的DC瘤苗(HIFU组)一次性免疫正常BALB/c小鼠,7d后再皮下接种活的CT-26结肠癌细胞,然后观察肿瘤发生时间、20d时瘤体重量和体积、小鼠生存时间等。并设立反复冻融法致敏DC组(冻融组)和生理盐水对照组(对照组),比较各组瘤体重量和体积、小鼠生存时间是否有差异。结果HIFU组、冻融组与对照组比较肿瘤发生时间、20d瘤体重量和体积、小鼠中位生存时间等差异均有统计学意义(P<0.01或P<0.05)。HIFU组与冻融组比较瘤体重量、体积及小鼠中位生存时间差异亦有统计学意义(P<0.05)。结论HIFU辐照法制备的DC瘤苗对小鼠肿瘤的发生有一定的主动免疫作用,并优于反复冻融法制备的DC瘤苗。     

树突状细胞疫苗在肝癌免疫治疗中的研究进展

肝癌是我国最常见的恶性肿瘤之一。目前,继手术、放疗、化疗之后,肝癌的免疫治疗已成为新的治疗手段。树突状细胞作为目前已知的体内功能最强的专职抗原递呈细胞,在机体抗肿瘤免疫反应中发挥着不可替代的作用。     

B7瘤苗与DC瘤苗诱导的抗L615白血病的免疫作用

目的 研究Ｂ７瘤苗的负载了肿瘤细胞膜抗原的ＤＣ瘤苗在小鼠Ｌ６１５白血病模型中诱导抗白血病免疫的作用。方法 通过观察小鼠的存活率和生存时间,研究两种瘤苗在动物体内诱导免疫预防保护的能力;通过体外细胞毒实验和细胞增殖实验,检测两种瘤苗在体外诱导的Ｔ细胞特异性杀伤活性及对特异性抗原刺激的增殖活性。结果 在体内,两种瘤苗免疫的小鼠对随后活瘤细胞的攻击均有保护作用,ＤＣ瘤苗效果更佳;同时还发现输注免疫保护鼠     

Current issues in dendritic cell cancer immunotherapy

Dendritic cells (DCs) initiate and direct the immune response. Their inability to detect danger signals from transformed cells and to generate an effective immunological response may allow cells with a malignant phenotype to evolve into cancers. This defect can be corrected for many cancer types and the immune response boosted to eliminate malignant cells by means of DC-based vaccines/therapies. Rapid advances in our understanding of basic DC physiology and improved methods for DC isolation have made clinical application of DC therapy practical, and encouraging phase I/II results are emerging.     

Clinical applications of dendritic cell vaccines

Dendritic cells play a central role in the presentation of antigen to na?ve T-cells and the induction of primary immune responses. Preclinical studies have established that dendritic cells loaded with antigens ex vivo induce potent antitumor and antiviral immune responses in vitro and in vivo. This has lead to a proliferation of clinical trials testing their effectiveness in humans, particularly with advanced malignancies. The few reported studies suggest that clinically relevant immune responses may be induced against some types of malignancies. Many questions regarding the best type of dendritic cell, degree of maturity, choice of antigen, route and schedule of administration, targeting to lymphoid tissue and use of additional adjuvants will need to be answered in preclinical and clinical studies as the field of dendritic cell-based immunotherapy progresses.     

Maximizing dendritic cell migration in cancer immunotherapy

Background: The success of dendritic cell (DC)-based immunotherapy in inducing cellular immunity against tumors is highly dependent on accurate delivery and trafficking of the DC to T-cell-rich areas of secondary lymphoid tissues. Objective: To provide an overview of DC migration in vivo and how migration to peripheral lymph nodes might be improved to optimize DC therapy. Methods: We focused on DC migration in preclinical models and human skin explants and on clinical vaccination trials studying migration of in vitro-generated DC. Results/conclusions: DC migration requires an intricate interplay between the cell and its environment. To maximize migration for cellular therapy, it is important to optimize the generation of migratory DC as well as treatment strategies.     

Dendritic cell fusion vaccines for cancer immunotherapy

The use of tumour vaccines is being explored as a means of generating effective antitumour immune responses in patients with cancer. Dendritic cells (DCs) are the most potent antigen-presenting cells that are essential for initiating primary immune responses. As such, DCs are being studied as a platform for the design of cancer vaccines. DCs loaded with tumour antigens or whole tumour cell derivatives stimulate tumour-specific immunity. A promising vaccine strategy involves the fusion of DCs with whole tumour cells. DC/tumour fusions express a broad array of tumour antigens, including those yet to be identified, in the context of DC-mediated costimulation. Animal models have demonstrated that vaccination with fusion cells is protective against tumour challenge and results in the regression of established metastatic disease. In vitro human studies have demonstrated that DC/tumour fusions potently stimulate antitumour immunity and lysis of autologous tumour cells. Vaccination of cancer patients with DC/tumour fusions is being studied in Phase I/II clinical trials. Preliminary results demonstrate that generation of a vaccine is feasible and that vaccination is associated with minimal toxicity. Immunological and clinical responses have been found in a subset of patients.     

Dendritic cell fusion vaccines for cancer immunotherapy

The use of tumour vaccines is being explored as a means of generating effective antitumour immune responses in patients with cancer. Dendritic cells (DCs) are the most potent antigen-presenting cells that are essential for initiating primary immune responses. As such, DCs are being studied as a p-latform for the design of cancer vaccines. DCs loaded with tumour antigens or whole tumour cell derivatives stimulate tumour-specific immunity. A p-romising vaccine strategy involves the fusion of DCs with whole tumour cells. DC/tumour fusions express a broad array of tumour antigens, including those yet to be identified, in the context of DC-mediated costimulation. An-imal models have demonstrated that vaccination with fusion cells is p-rotective against tumour challenge and results in the regression of es-tablished metastatic disease. In vitro human studies have demonstrated that DC/tumour fusions potently stimulate antitumour immunity and lysis of autologous tumour cells. Vaccination of cancer patients with DC/tumour fusions is being studied in Phase I/II clinical trials. Preliminary results demonstrate that generation of a vaccine is feasible and that vaccination is associated with minimal toxicity. Immunological and clinical responses have been found in a subset of patients.     

Closed system generation of dendritic cells from a single blood volume for clinical application in immunotherapy

Dendritic cells (DC) used for clinical trials should be processed on a large scale conforming to current good manufacturing practice (cGMP) guidelines. The aim of this study was to develop a protocol for clinical grade generation of immature DC in a closed-system. Aphereses were performed with the Cobe Spectra continuous flow cell separator and material was derived from one volume of blood processed. Optimisation of a 3-phase collection autoPBSC technique significantly improved the quality of the initial mononuclear cell (MNC) product. Monocytes were then enriched from MNC by immunomagnetic depletion of CD19+ B cells and CD2+ T cells and partial depletion of NK cells using the Isolex 300I Magnetic cell selector. The quality of the initial mononuclear cell product was found to determine the outcome of monocyte enrichment. Enriched monocytes were cultured in Opticyte gas-permeable containers using CellGro serum-free medium supplemented with GM-CSF and IL-4 to generate immature DC. A seeding concentration of 1 x 10(6) was found optimal in terms of DC phenotype expression, monocyte percentage in culture, and cell viability. The differentiation pattern favours day 7 for harvest of immature DC. DC recovery, viability, as well as phenotype expression after cryopreservation of immature DC was considered in this study. DC were induced to maturation and evaluated in FACS analysis for phenotype expression and proliferation assays. Mature DC were able to generate an allogeneic T-cell response as well as an anti-CMV response as detected by proliferation assays. These data indicate that the described large-scale GMP-compatible system results in the generation of stable DC derived from one volume of blood processed, which are qualitatively and quantitatively sufficient for clinical application in immunotherapeutic protocols.     

树突细胞应用于荷白血病小鼠免疫治疗的实验研究

目的探讨白血病抗原活化的树突细胞(DC)应用于荷白血病小鼠异基因骨髓移植 (allo-BMT)后免疫治疗的可行性及有效性。方法应用mGM-CSF及mIl-4从小鼠骨髓细胞扩增出成熟DC,使其负载经冻融法制备的L7212白血病细胞相关抗原。将进行allo-BMT后的荷白血病小鼠分 A(对照组)、B(T细胞组)、C(DC T细胞组)三组进行免疫治疗,观察小鼠生存率、生存期、移植物抗宿主病(GVHD)发生等情况及血清细胞因子水平和脾细胞细胞毒活力变化。对各组长期生存小鼠行二次攻击,以观察其体内抗白血病免疫能力。结果小鼠骨髓单个核细胞经mGM-CSF、mIL-4联合作用7 d可生成大量成熟DC。B、C二组复发率分别为30％及0％,移植后长期生存率分别为30％及 70％,两组差异均有统计学意义(P<0．05),而GVHD发生率差异无统计学意义。两组平均生存时间分别为(32．95±13．29)d、(41．15±13．88)d,差异有统计学意义(P<0．01)。MYT法检测发现C组小鼠脾细胞对L7212细胞产生特异性杀伤作用;EIJSA法检测显示血清中Th1类因子IL-2水平为 (419．75±26．66)pg／ml,明显高于其他两组(P<0．01)。二次攻击后B、C二组生存率分别为33．3％及85．7％,差异有统计学意义(P<0．05)。结论肿瘤抗原负载的DC联合供者淋巴细胞输注是增强 allo-BMT后移植物抗白血病效应、减少白血病复发的有效手段。     

Recent clinical development of dendritic cell-based immunotherapy for prostate cancer

Dendritic cells (DCs) are the most powerful immune cells that present antigens to T cells, resulting in a T cell response. Therapeutic strategies involving DCs have been explored in many malignancies, including prostate cancer. These strategies are designed to stimulate DC proliferation, promote antigen uptake and processing by DCs, or to directly provide antigen-loaded DCs. All approaches are designed to stimulate an antitumour T cell response leading to clinical benefit. Many approaches in prostate cancer have demonstrated successful induction of the desired immune response. Clinical effect has also been observed, prompting larger definitive trials.