NK细胞杀伤人骨髓瘤RPMI8226细胞的活性及其可能的机制

目的:研究同种异体NK细胞对人骨髓瘤RPMI 8226细胞的杀伤活性及其可能的机制。方法:LDH释放法检测NK细胞对RPMI 8226细胞和人白血病K562细胞的杀伤活性,流式细胞术和RT-PCR法分别检测K562和RPMI 8226细胞中NKG2D配体和HLA-Ⅰ类分子的表达;阻断K562和RPMI 8226细胞中NKG2D配体的表达后,检测NK细胞的杀伤活性。结果:NK细胞对RPMI 8226靶细胞的杀伤活性明显低于对K562靶细胞的杀伤(P<0.01)。K562细胞高表达NKG2D配体,不表达HLA-Ⅰ类分子;RPMI 8226细胞低表达NKG2D配体,高表达HLA-Ⅰ类分子,其HLA基因型为A 01,66;B 58,58;Cw 03,06。阻断NKG2D配体后NK细胞杀伤K562细胞的活性明显降低(P<0.01),而杀伤RPMI 8226细胞的活性无明显改变;阻断HLA-Ⅰ类分子,NK细胞杀伤K562细胞的活性无变化,而杀伤RPMI 8226细胞的活性明显提高(P<0.01)。结论:NK细胞杀伤RPMI 8226细胞的活性较低,其机制与RPMI 8226细胞高表达HLA-Ⅰ类分子、低表达NKG2D配体有关。     

茶多酚诱导人多发性骨髓瘤RPMI8226细胞的凋亡及其作用机制

目的:研究茶多酚对人多发性骨髓瘤RPMI 8226细胞生长及凋亡的影响,并探讨其可能的作用机制.方法:通过MTT法、瑞氏染色法和FCM法分别检测不同浓度的茶多酚对RPMI 8226细胞增殖和凋亡的影响;FCM法检测对细胞线粒体膜电位的影响;蛋白质印迹法检测△caspase-3片段和凋亡相关蛋白bc1-2的表达;ELISA法检测对RPMI 8226细胞分泌细胞因子白细胞介素-6(interleukin-6,IL-6)水平的影响.结果:与对照组相比,茶多酚浓度129.6和259.1 μmol/L处理RPMI 8226细胞1～3 d后均能明显抑制细胞的增殖,且呈时间-剂量相关性;统计显示,24 h时的半数细胞抑制浓度(half inhibitory concentration,IC50)值为165.7μmol/L.茶多酚(129.6μmol/L)作用24 h后,RPMI 8226细胞出现典型的凋亡形态学改变;茶多酚(129.6和259.1 μmol/L)作用24 h后,RPMI 8226细胞凋亡率分别为(24.6±2.3)％和(43.5±3.9)％,与对照组比较差异均有统计学意义;细胞的线粒体膜电位降低,活性△caspase-3片段产生,bc1-2蛋白表达水平下降,IL-6分泌水平降低.结论:茶多酚能抑制RPMI 8226细胞增殖并诱导其凋亡,其作用机制可能与产生活性△caspase-3片段,抑制bc1-2蛋白表达,降低细胞分泌IL-6水平相关.     

硼替佐米联合NK细胞对骨髓瘤细胞株KM-3作用的影响

目的:探讨硼替佐米联合自然杀伤(NK)细胞杀伤及诱导多发性骨髓瘤细胞株KM-3凋亡的作用.方法:WST-1法观察加入硼替佐米后,NK细胞对KM-3细胞杀伤作用的变化;Annexin-V、PI及CD45三重免疫荧光标记,流式细胞术检测Annexin-V+/PI凋亡细胞及线粒体跨膜电位的变化.结果:效靶比为5:1、10:1和20:1的NK细胞联合5 nmol/L硼替佐米处理后12、24和48 h,均显著杀伤KM-3细胞(P=0.003),杀伤率的升高呈时间依赖性(P=0.002),且显著高于NK细胞单独处理,P<0.01.效靶比为5:1、10:1和20:1的NK细胞联合5 nmol/L硼替佐米处理,Annexin-V+/PI-细胞比例均增加(P=0.003),呈时间依赖性(P=0.002),且高于NK细胞单独处理,P<0.01.效靶比为5:1、10:1和20:1的NK细胞联合5 nmol/L硼替佐米处理后6、12和24 h,KM-3细胞线粒体跨膜电位明显降低(P=0.025),呈时间依赖性(P=0.022),且低于NK细胞单独处理,P<0.05.结论:硼替佐米联合NK细胞具有更显著地杀伤并诱导KM-3细胞凋亡的作用,提示硼替佐米与NK细胞具有协同作用.     

蛇床子素诱导人多发性骨髓瘤 RPMI －8226细胞凋亡及其机制研究

目的：研究蛇床子素（Osthole）的抗骨髓瘤作用,并探讨其抗骨髓瘤的作用机制。方法：处于对数增殖期人多发性骨髓瘤细胞 RPMI －8226随机分为空白对照组及10、20、40、80、120、160和200μmol／L Osthole组,用 MTT 法检测细胞增殖率,采用 Western blot 法检测凋亡相关蛋白表达量。结果：细胞培养24、48和72h后,不同浓度 Osthole 组细胞增殖数显著低于空白对照组,且作用呈剂量依赖性。不同浓度 Osthole 组细胞凋亡相关蛋白 PARP 被切割明显高于对照组,p53蛋白的表达量明显高于对照组,抗凋亡蛋白 Mcl －1表达明显下降。结论：Osthole 能明显抑制人多发性骨髓瘤细胞 RPMI －8226细胞增殖,分子机制可能是诱导其细胞凋亡,其诱导凋亡的机制有待于进一步深入研究。     

三氧化二砷诱导人骨髓瘤细胞RPMI 8226凋亡的机制探讨

目的:探讨三氧化二砷（As2O3）诱导人骨髓瘤细胞RPMI 8226凋亡的机制。方法:不同浓度As2O3作用RPMI 8226细胞48h后,用MTT法计算细胞增殖抑制率。流式细胞仪检测1.0、2.0、5.0μmol/L As2O3干预RPMI 8226细胞48h后的凋亡率;透射电镜观察As2O3作用前后RPMI 8226细胞超微结构的变化;RT-PCR、Western Blot法检测As2O3作用前后Bcl-2及Caspase-3表达的变化。结果:不同浓度的As2O3对RPMI 8226细胞均有增殖抑制作用(P<0.05）。1.0、2.0、5.0μmol/L As2O3干预RPMI 8226细胞48h后,细胞凋亡率随As2O3浓度的增加而呈上升趋势,与对照组相比,差异具有统计学意义（P<0.05）;As2O3干预RPMI 8226细胞48h后,电镜下可见典型的凋亡小体;RT-PCR、Western Blot结果均显示上述浓度的As2O3干预RPMI 8226细胞48h后,Bcl-2 mRNA及蛋白表达下调（P<0.05）,Caspase-3 mRNA及蛋白表达上调（P<0.05）。结论:As2O3可能通过激活Caspase-3、下调Bcl-2的表达从而诱导RPMI 8226细胞凋亡。     

黄连解毒汤抑制多发性骨髓瘤RPMI8226细胞增生及促凋亡作用的研究

 目的 研究中药黄连解毒汤（HLJDT）对人多发性骨髓瘤（MM）细胞RPMI8226增生和凋亡的作用。方法 以含10 ％胎牛血清的RPMI1640培养基常规培养RPMI8226细胞,分别以不同浓度的HLJDT作用不同的时间后,应用锥虫蓝拒染法测定细胞活力变化,MTT法检测细胞的增生变化;采用流式细胞术测定细胞周期的变化;应用流式细胞仪检测药物细胞的凋亡现象,荧光显微镜下观察AO／EB染色后的细胞凋亡形态变化;比色法检测半胱氨酸蛋白水解酶3（caspase3）活性变化。结果 与对照组相比,200～800 ng／ml浓度的HLJDT可明显抑制细胞增生影响（P＜0.01）,并呈时间和剂量依赖性;使细胞周期阻滞在G0／G1期细胞增多,S期细胞减少,并呈剂量依赖性改变; MM细胞凋亡百分率显著增高（P＜0.01）,免疫荧光显微镜下可见典型的凋亡细胞形态学变化;使caspase3活性增强,且呈剂量和时间依赖性（P＜0.01）。结论 HLJDT能有效抑制MM细胞RPMI8226增生,促其凋亡,G0／G1期细胞比例增加和S期细胞比例减少可能是原因之一;caspase3活性增强可能参与其凋亡过程,具体机制研究还有待完善。     

NK细胞抗肿瘤免疫效应机制研究进展

自然杀伤(NK)细胞无需抗原预先致敏即可直接杀伤靶细胞，通常被视为机体免疫防御系统的第一道防线。NK细胞主要通过诱导靶细胞凋亡、释放效应细胞冈子、介导抗体依赖性细胞毒性(ADCC)作用等途径杀伤肿瘤细胞。现综述近年来NK细胞在以上效应机制方面的研究进展。     

依托泊苷对人骨髓瘤细胞 RPMI8226增殖与凋亡的影响

目的：探讨依托泊苷对人骨髓瘤细胞 RPMI8226的增殖抑制作用及其分子机制。方法：将依托泊苷作用于骨髓瘤细胞,用 MTT 法检测细胞增殖抑制率,光学显微镜和电子显微镜观察细胞形态及超微结构变化,流式细胞术检测细胞凋亡率和细胞周期分布,半定量 RT －PCR 检测 Bax 及 Caspase －3 mRNA 表达量的变化,Western blot 检测 Bax 及 Caspase －3蛋白表达量变化。结果：依托泊苷可抑制 RPMI8226细胞增殖,抑制率呈时间（r ＝0．926）和浓度（r ＝0．938）依赖性增强。24h 后在光学显微镜下可见依托泊苷组细胞数量减少,排列紊乱,细胞形态变得不规则,可见凋亡细胞及坏死细胞。48h 电子显微镜下可见细胞典型凋亡改变,凋亡小体形成。流式细胞术检测结果显示,依托泊苷组 RPMI8226细胞凋亡率明显增高（P ＜0．05）;依托泊苷作用48h 后将 RPMI8226细胞阻滞于 S 期（P ＜0．05）;依托泊苷作用48h,Bax、Caspase －3 mRNA 及蛋白表达量增加（P ＜0．05）。结论：依托泊苷可诱导 RPMI8226细胞凋亡,可能与细胞周期阻滞,激活细胞内、外源性凋亡通路有关。     

人骨髓瘤细胞RPMI 8226的生物学特性

目的观察人骨髓瘤细胞RPMI 8226的生物学特性。方法光镜下观察RPMI 8226细胞形态、生长特点、体外克隆形成率;流式细胞仪分析其免疫表型、周期分布、多药耐药蛋白P-170和ABCG2的表达情况;MTT法分析其药物敏感性;PCR-SSP法检测HLA-Ⅰ类分子基因型;动物实验观察成瘤情况。结果 RPMI 8226细胞呈圆形,悬浮生长,细胞体积较大,细胞群体倍增时间为24.48 h。14 d和21 d时的克隆形成率分别为（10.27&#177;1.38）%、（42.56&#177;2.98）%。RPMI 8226细胞表达CD38、CD138和CD49e,不表达CD20、CD19、CD11a、CD3、CD13、κ、λ。RPMI 8226细胞周期为：G0/G1期细胞占（57.64&#177;2.31）%,S期细胞占（35.75&#177;1.18）%、G2/M期细胞占（6.73&#177;0.21）%;P-170和ABCG2表达率分别为（2.27&#177;0.35）%、（1.33&#177;0.26）%。RPMI 8226细胞对ADM、VCR、DDP、VP16和MMC药物的IC50分别为（0.56&#177;0.06）、（0.92&#177;0.10）、（1.17&#177;0.32）、（1.83&#177;0.16）和（4.91&#177;0.84）μmol/L。染色体数目在43－49之间。HLA-Ⅰ基因型为A19,19;B 15,37;Cw02,02。BALB/c裸鼠皮下接种1&#215;107个细胞可以成瘤,病理证实为浆细胞瘤。结论 RPMI 8226细胞具有多发性骨髓瘤细胞的特点,可以用于基础和临床研究。     

多发性骨髓瘤细胞株PRIM8226侧群细胞分选及其生物学特性的研究

目的 检测和分选多发性骨髓瘤（MM）细胞株PRIM8226中的侧群细胞（SP细胞）并鉴定其生物学特性.方法 以Hoechst33342/碘化丙啶（PI）荧光染料双染,维拉帕米拮抗对照,应用流式细胞术荧光激活分选法检测并分选MM细胞株PRIM8226 SP细胞,并通过细胞生长曲线、细胞周期、免疫表型、集落形成实验、RT-PCR检测干细胞特异标志物mRNA表达量、裸鼠体内成瘤实验等对SP细胞的生物学特性进行初步探讨.结果 MM细胞株PRIM8226 SP细胞含量为（1.78±0.89）％,采用流式细胞术成功分选SP细胞.生长曲线显示：SP细胞分选初期生长较主群细胞（MP细胞）缓慢,进入稳定增长期后增殖能力与MP细胞差异无统计学意义（P＞0.05）.细胞周期分析显示：SP细胞与MP细胞相比,周期多处于Go/G1期[（44.34±3.09）％、（28.49±1.97）％,P＜0.05],较少的细胞处于S期[（38.83±3.69）％、（51.49±4.62）％,P＜ 0.05].在免疫表型研究中,观察到SP和MP细胞的CD138、CD38表达分别为（78.5±8.5）％、（82.0±4.0）％和（72.3±15.7）％、（84.3±11.9）％,差异均无统计学意义（均P＞0.05）.MM细胞株PRIM8226 SP细胞的单细胞克隆直径、克隆形成数、克隆形成率均高于MP细胞[0.280±0.016和0.118±0.019、1 722±127和358±14、（86.1±3.46）％和（17.9±1.88）％,P＜0.05].RT-PCR显示SP细胞干细胞标志性基因的表达高于MP细胞：c-myc[（29.90±3.73）％、（16.84±2.35）％]、KIF4[（29.97±2.89）％、（19.06±1.23）％]、SOX2[（40.00±4.58）％、（16.62±2.09）％]、OCT4[（32.96±1.56）％、（23.27±0.92）％]（均P＜0.05）.裸鼠体内成瘤实验显示SP细胞成瘤能力显著高于MP细胞（最低成瘤数量分别为5×103、5×105个）.结论 MM细胞株PRIM8226的SP细胞在静止期细胞比例、集落形成能力、干细胞标记c-myc、KIF4、SOX2、OCT4基因表达量、体内成瘤能力上与MP细胞差异均有统计学意义,而SP细胞和MP?     

The frequency of T regulatory cells modulates the survival of multiple myeloma patients: detailed characterisation of immune status in multiple myeloma

Background:

Multiple myeloma (MM) is an immunoproliferative disease characterised by the uncontrolled proliferation of plasma cells, which is accompanied by defects in the immune system.

Methods:

This study aimed to characterise the frequency of T regulatory cells (Tregs), dendritic cells (DCs) as well as sub-populations of T cells bearing regulatory properties like CD4⁺GITR⁺, CD4⁺CD62L⁺, CD3⁺TCRγδ⁺ along with the concentrations of IL-10, TGFβ, IL-6 in 66 patients with MM. Subsequently, the influence of therapy on those components of immune system was assessed.

Results:

The percentage of both myeloid and plasmacytoid DC was lower in MM compared with control group while Treg (CD4⁺CD25^highFOXP3⁺) frequencies were significantly higher in MM patients compared with healthy control (6.16% vs 0.05%, respectively). Also, the percentages of CD4⁺GITR⁺, CD4⁺CD62L⁺ were increased compared with healthy volunteers. We found that patients with higher percentages of Treg live shorter (median overall survival 21 months vs not-reached, P=0.013).

Conclusion:

This study identifies several abnormalities of immune system in MM, which only partly could be normalised after successful therapy. The dysfunction of immune system such as decreased antigen presentation along with increased frequencies of suppressive cells and cytokines might facilitate progression of the disease and infectious complications limiting survival of MM patients.     

Dendritic cell vaccines in the treatment of multiple myeloma: advances and limitations

Dendritic cells (DCs) are antigen-presenting cells that play a key role in the induction of cytotoxic T-lymphocytes. Adjuvant immunotherapy with antigen-loaded DCs represents an attractive anticancer strategy for multiple myeloma (MM). Autologous DCs loaded with idiotypic protein or other myeloma-associated antigen have been used in several clinical trials. Preclinical and first clinical experience have provided valuable insights in the mechanisms of cellular immunity, but few, if any, patients with MM benefited from such vaccination. Taken together, the data suggest that antitumor T-cell responses fail in MM because of a deregulated cytokine network, downregulation of costimulatory surface receptor expression, and changes in T-cell repertoire, enabling tumor cells to escape immune effectors by preventing the antitumor imune response. We discuss current clinical protocols for DC-based immunotherapy in MM and review some strategies that may increase the efficacy of DC vaccines.     

恶性肿瘤的代谢与免疫逃逸

恶性肿瘤的发生发展意味着肿瘤细胞适应了不利的环境。肿瘤细胞代谢往往降低线粒体活性和氧化磷酸化过程,在很大程度上依赖有氧糖酵解产生能量。这特定的新陈代谢造成肿瘤微环境的变化,帮助肿瘤细胞得以生存、转移及免疫逃逸,而免疫逃逸包括抑制和阻断肿瘤的免疫反应。这一效应通过许多机制实现,包括肿瘤代谢过程及代谢产物对免疫系统直接和间接的抑制和阻断作用。     

BCMA CAR-T细胞治疗的耐药机制及优化策略研究

嵌合抗原受体T细胞（chimeric antigen receptor T cells,CAR-T）疗法在血液系统肿瘤治疗中已展示出卓越成效。BCMA抗原在骨髓瘤细胞表面普遍表达,是合适高效的CAR-T治疗靶抗原。尤其是对于复发/难治性多发性骨髓瘤患者,BCMA CAR-T细胞治疗缓解率高,多数患者在输注1年后仍可在体内检测到CAR-T细胞。但是耐药与疾病复发仍是目前临床管理中面对的关键问题。本文将从多发性骨髓瘤细胞免疫逃逸、CAR-T产品因素、既往治疗方案及肿瘤免疫微环境的抑制等几个方面来探讨BCMA CAR-T细胞疗法的应答响应因素及耐药诱导机制,并提出可能的优化策略,以期为未来探索提供参考意义。     

As2O3对多发性骨髓瘤细胞的细胞毒作用的机制研究

背景与目的:多发性骨髓瘤(multiple myeloma,MM)是恶性浆细胞疾病,目前仍难以治愈;已有研究证明三氧化二砷(arsenic trioxide,As2O3)在体外能够抑制骨髓瘤细胞增殖并诱导其凋亡.本研究拟探讨As2O3对多发性骨髓瘤细胞的可能作用机制.方法:采用MTr法检测As2O3对5株骨髓瘤细胞U266、SKO-007、LP-1、HS-Sultan和KM3的抑制作用,求出其IC50,同时研究维生素K3(vitamine K3,VK3)、N-乙酰半胱氨酸(N-acetyl-cysteine,NAC)和还原型谷胱甘肽(glutathione,GSH)对As2O3的协同或拮抗作用;利用光学比色法测定不同浓度As2O3作用后的5株骨髓瘤细胞以及As2O3与VK3、NAC或外源性GSH共同作用后的U266细胞的GSH含量,对细胞GSH含量与IC50进行相关性分析.结果:As2O3对5株骨髓瘤细胞均有增殖抑制作用,但其敏感性不同,细胞内GSH含量与其IC50正相关(r=0.87,P＜0.05);氧化剂VK3与As2O3有明显协同作用,抗氧化剂NAC和GSH对As2O3具有拮抗作用.结论:As2O3可能是通过与细胞内的含巯基化合物结合,降低细胞内GSH含量,从而诱导骨髓瘤细胞凋亡.     

Effects of Arsenic Trioxide Alone and in Combination with Bortezomib in Multiple Myeloma RPMI 8266 Cells

The aim of this study was to detect the efficiency of arsenic trioxide (ATO) alone or together with bortezomibto inhibit proliferation and induce apoptosis in a multiple myeloma (MM) RPMI 8266 cells. Mechanisms of actionwere also investigated. RPMI 8266 cells were treated with ATO alone and in combination with bortezomib for24 hours, and cell viability was assessed by modified MTT. Annexin V-F1TC and PI staining was used to detectthe apoptosis rate and cell cycling was investigated by flow cytometry, along with expression of cell surfacedeath receptor-4(DR4) and death receptor-5 (DR5). Western blotting was applied to detect the expression ofbcl-2, caspase-3, caspase-8, and caspase-9. As a result, the ATO combined with bortezomib group showed moreinhibition of RPMI 8266 cell viability than theATO group. Expression of DR4 and DR5 on the cell surfaces,and the apoptosis rate were increased after treatment by ATO alone or combined with bortezomib. The cellsappeared to arrest in G2/M phase after treatment. Expression of bcl-2 was more significantly decreased in thecombination group, and that of caspase-3, caspase-8 and caspase-9 was significantly increased as well. Therefore,bortezomib can enhance ATO actions to induce apoptosis in RPMI 8266 cells, with decrease in expression ofbcl-2 and increase of caspase-3, caspase-8 and caspase-9 proteins.     

Induction of myeloma-specific cytotoxic T lymphocytes responses by natural killer cells stimulated-dendritic cells in patients with multiple myeloma

The interaction between dendritic cells (DCs) and natural killer (NK) cells plays a key role in inducing DC maturation for subsequent T-cell priming. We investigated to generate potent DCs by stimulated with NK cells to induce myeloma-specific cytotoxic T lymphocytes (CTLs). NK cells-stimulated-DCs exhibited high expression of costimulatory molecules and high production of IL-12p70. These DCs induce high potency of Th1 polarization and exhibit a high ability to generate myeloma-specific CTLs responses. These results suggest that functionally potent DCs can be generated by stimulation with NK cells and may provide an effective source of DC-based immunotherapy in multiple myeloma.     

Immunotherapy based on bispecific T‐cell engager with hIgG1 Fc sequence as a new therapeutic strategy in multiple myeloma

Bispecific antibodies play an important role in immunotherapy. They have received intense interest from pharmaceutical enterprises. The first antibody drug, OKT3 (muromonab‐CD3), showed great performance in clinical treatment. We have successfully developed a single‐chain variable fragment (ScFv) combination of anti‐CD3 ScFv and anti‐CD138 ScFv with the hIgG1 Fc (hIgFc) sequence. The novel bispecific T‐cell engager (BiTE) with an additional hIgFc (BiTE‐hIgFc, STL001) can target T cells, natural killer cells, and multiple myeloma cells (RPMI‐8226 or U266). In addition, BiTE‐hIgFc (STL001) has nanomolar‐level affinity to recombinant human CD138 protein and shows more potent antitumor activity against RPMI‐8226 cells than that of separate aCD3‐ScFv‐hIgFc and aCD138‐ScFv‐hIgFc, or the isotype mAb in vitro or in vivo.     

Dendritic cell biology and the application of dendritic cells to immunotherapy of multiple myeloma

Dendritic cells (DCs) are extremely efficient antigen-presenting cells that are potent stimulators of both B and T cell immune responses. Although DCs are normally present in extremely small numbers in the circulation, recent advances in DC biology have made it possible to generate DCs in culture. DCs can be generatedin vitro from various cellular sources including bone marrow, cord blood and peripheral blood. Although culture conditions are extremely diverse, the majority of protocols grow DCs in GM-CSF and either TNF-alpha and/or IL-4. The addition of other growth factors such as SCF and Flt-3 ligand can dramatically enhance DC recovery. It is important to appreciate that DC subsets have been identified. Thus, DC at different stages of maturation, based on phenotype and capacity to capture antigen, can be obtained depending on culture conditions. For clinical applications, DCs can be generated in serum-free media and cryopreserved for future clinical applications. The ability to obtain DCs in numbers suitable for manipulating immune responses has pushed DC-based immunotherapies into the spotlight for treatment of various malignancies, including multiple myeloma, a B cell malignancy that is presently incurable. Although high-dose chemotherapy and transplantation have improved complete remission rates and overall survival in myeloma, immunotherapeutic strategies are needed for the additional cytoreduction needed to achieve a cure. Because DCs specialize in antigen capture and are extremely potent at stimulating T cell responses, they are ideally suited for generating anti-myeloma T cell responsesin vivo. Several studies have demonstrated that myeloma protein, also called idiotype (Id), is sufficiently immunogenic and can be used to generatein vivo T cell responses in myeloma patients. Clinical trials using Id-pulsed DCs as a vaccine to treat minimal residual disease or relapsed myeloma are currently underway. Feasibility studies indicate that antigen-pulsed autologous DCs can be used to elicitin vivo Id-specific T cell responses. Additional studies are needed to optimize current DC vaccination protocols and determine clinical benefits associated with this approach. It is hoped that, following conventional therapies, a combination of adoptive immunotherapeutic modalities such as DCs together with myeloma-specific T cells may lead to improved clinical responses in multiple myeloma, and ultimately lead to complete remission and cure.