Study protocol of the Asian XELIRI ProjecT(AXEPT):a multinational,randomized,non-inferiority,phase Ⅲ trial of second-line chemotherapy for metastatic colorectal cancer, comparing the eicacy and safety of XELIRI with or without bevacizumab versus FOLFIRI w

Background: Capecitabine and irinotecan combination therapy(XELIRI) has been examined at various dose levels to treat metastatic colorectal cancer(m CRC). Recently, in the Association of Medical Oncology of the German Cancer Society(AIO) 0604 trial, tri?weekly XELIRI plus bevacizumab, with reduced doses of irinotecan(200 mg/m^2 on day 1) and capecitabine(1600 mg/m^2 on days 1–14), repeated every 3 weeks, has shown favorable tolerability and eicacy which were comparable to those of capecitabine and oxaliplatin(XELOX) plus bevacizumab. The doses of capecit?abine and irinotecan in the AIO trial are considered optimal. In a phase I/II study, XELIRI plus bevacizumab(BIX) as second?line chemotherapy was well tolerated and had promising eicacy in Japanese patients.Methods: The Asian XELIRI Projec T(AXEPT) is an East Asian collaborative, open?labelled, randomized, phase Ⅲ clinical trial which was designed to demonstrate the non?inferiority of XELIRI with or without bevacizumab versus standard FOLFIRI(5?fluorouracil, leucovorin, and irinotecan combination) with or without bevacizumab as second?line chemo?therapy for patients with m CRC. Patients with 20 years of age or older, histologically conirmed m CRC, Eastern Coop?erative Oncology Group performance status 0–2, adequate organ function, and disease progression or intolerance of the irst?line regimen will be eligible. Patients will be randomized(1:1) to receive standard FOLFIRI with or with?out bevacizumab(5 mg/kg on day 1), repeated every 2 weeks(FOLIRI arm) or XELIRI with or without bevacizumab(7.5 mg/kg on day 1), repeated every 3 weeks(XELIRI arm). A total of 464 events were estimated as necessary to show non?inferiority with a power of 80% at a one?sided α of 0.025, requiring a target sample size of 600 patients. The 95% conidence interval(CI) upper limit of the hazard ratio was pre?speciied as less than 1.3.Conclusion: The Asian XELIRI Projec T is a multinational phase III trial being conducted to provide evidence for XELIRI with or without bevacizumab as a second?line treatment option of mCRC.

The safety parameters of the study on intraductal cytotoxic agent delivery to the breast before mastectomy

Background： Intraductal administration of cytotoxic agents has been shown to inhibit the development of breast cancer in animal models. The object of this study was to demonstrate the safety of intraductal delivery cytotoxic agents in patients prior to mastectomy. This method is hopeful to be developed as a chemoprevention approach in patients with pre-malignant or non-invasive ductal lesions to prevent breast cancer which will be further developed.Methods： Two drugs, pegylated liposomal doxorubicin（PLD） and carboplatin were administered at three dose levels（PLD： 10, 20, 50 mg and carboplatin 60, 120, 300 mg）. There were five subjects in each group with 15 subjects treated with each drug once. Venous blood samples were obtained for pharmacokinetic analysis. The breast was removed surgically 2-5 days post administration and the treated ducts were marked to enable identification on pathological evaluation. Results： Intraductal administration was generally well-tolerated with mild, transient breast discomfort. In the carboplatin arm, three women at the 300 mg dose experienced mild nausea and vomiting. In the PLD arm most women had mild erythema and swelling of the breast over the 72 hours following the drug administration. Patients receiving the 50 mg dose experienced local erythema until the time of surgery. Pharmacokinetic analysis showed that carboplatin rapidly entered systemic circulation with an early peak time（T max -30 min） with a corresponding plasma ultrafiltrate area under the curve（AUC） consistent with the Calvert Formula using estimated glomerular filtration rate（GFR）. Total plasma doxorubicin had delayed peak concentration times（T max 48 hours） with a linear dose response and peak concentrations substantially lower than expected from equivalent intravenous injection dosing. No doxorubicinol metabolite was detected in the plasma. Conclusions： This study demonstrates that cytotoxic drugs can be safely administered into breast ducts with minimal toxicity.

Cytotoxic effect of a non-peptidic small molecular inhibitor of the p53-HDM2 interaction on tumor cells

AIM: To investigate if non-peptidic small molecular inhibitors of the p53-HDM2 interaction could restore p53 function and kill tumor cells.METHODS: A series of non-peptidic small HDM2 inhibitors were designed by computer-aided model and synthesized by chemical method. Syl-155 was one of these inhibitors. Cytotoxic effect of syl-155 on three tumor cell lines with various states of p53, HT1080 (wild-type p53), KYSE510 (mutant p53), MG63 (p53 deficiency) was evaluated by MTT assay, Western blot and flow cytometry.RESULTS: Syl-155 stimulated the accumulation of p53 and p21 protein in HT1080 cells expressing wild-type p53, but not in KYSE510 and MG63 cells. Consequently, syl-155 induced cell cycle arrest and apoptosis in HT1080 cells.CONCLUSION: Non-peptidic small molecular inhibitors of the p53-HDM2 interaction show promise in treatment of tumors expressing wild-type p53.

Combined therapeutic effects of cytotoxic agent and differentiation-inducer on human gastric carcinoma cell line SGC-7901

Objective:To study the combined therapeutic effects of cytotoxic agent and differentiation-inducer on human gas tric carcinoma celll line SGC-7901 in vitro. Methods: The combined therapeutic effects of all-trans retinoic acid (ATRA), interferon a (IFNa)and fluorouracil (5-Fu) on gastric carcinoma cell line ax 7901 were observed when one of the 3, the combination of any 2 of the 3 and combination of all the 3 were administered respectively. The morphological and functional changes of gastric carcinoma cells were studied with MTT assay, flow cytometry, image analysis and determination of CEA content in the culture medium of the cells. Results: The cytostatic rate was increased as shown by the decrease of the rate of colony formation of the cells on culture disc when one agent, the combination of 2 agents and the combination of the 3 were administered progressively. The cells were relatively accumulated in the phase of G0/G1 and synthesis of DNA in he cells was inhibited.The malignant phenotype of the cells disappeared gradually while the characteristics of matUre cells were in creased. Meanwhile, CEA Level in the culture medium was decreased progressively. Apoptosis of the cells was oborved and a large amount of apoptotic apoptotic were found. Conclusion: The administration of the 3 agents in combination result in signif icant inhibition on proliferation, inducing of differention and promotion of apoptosis of gastric caxcinoma cells. The combina tion of cytotoxic agent and differention-inducer exerts significant inhibition on gastric carcinoma cells in vitro.

A Small Amino Acid, Big Impact: Methionine Restriction in Cancer Therapy

A recent study published in Gut(doi:10.1136/gutjnl-2022-326928)reveals a novel potential strategy for cancer immunotherapy:a methioninerestricted diet(MRD).A research team,led by Dr.JU Huaiqiang and Dr.XU Ruihua from the Sun Yat-sen University Cancer Center,and Dr.PIAO Hailong from the CAS Dalian Institute of Chemical Physics(DICP),discovered that a diet deficient in methionine,an essential amino acid,can reduce tumor growth and boost antitumor immunity.This is achieved by increasing the number and cytotoxicity of tumor-infiltrating CD8+T cells,a type of immune cell that plays a crucial role in fighting cancer.

晚期喉癌药物治疗的研究进展

喉癌是头颈部最常见的恶性肿瘤之一,大多数喉癌患者在确诊时已经处于晚期,预后通常较差,虽然切除全喉的手术治疗配合高强度放射治疗为喉癌患者提供了癌症治愈的机会,但切除全喉后可能导致患者失去语音能力、改变呼吸通道等,严重影响患者的生活质量。随着国内外喉癌治疗的不断深入研究,新的治疗技术如诱导化疗、放化同步治疗和生物治疗已经相继问世。本文通过对用于喉癌治疗的药物进行了综述,旨在为临床治疗提供借鉴。

氮掺杂姜黄素碳点光热治疗肺癌细胞

以姜黄素、柠檬酸和分支聚乙烯亚胺为前驱物,通过溶剂热法制备具有高光热效应的氮掺杂姜黄素碳点(Cur-CD),用于光热杀灭肺癌细胞。利用透射电子显微镜、X射线衍射光谱、傅里叶红外光谱、X射线电子能谱、Raman光谱研究Cur-CD的形态和组成;利用紫外、荧光分光光度计探究Cur-CD的光学性能;通过波长808 nm近红外激光照射探究Cur-CD的光热性能;通过细胞实验探究Cur-CD的细胞毒性、摄取和成像以及细胞光热治疗能力。成功制备了具有良好荧光性能和光热转换效率的氮掺杂Cur-CD,制备的Cur-CD在较低质量浓度就能在肿瘤细胞中累积并产生荧光,对癌细胞有毒性并且能将近红外光能转换成热能,从而有效杀灭肿瘤细胞。

Chemotherapy for hepatocellular carcinoma:The present and the future

Hepatocellular carcinoma(HCC) is the most common primary tumor of the liver. Its relationship to chronic liver diseases, in particular cirrhosis, develops on a background of viral hepatitis, excessive alcohol intake or metabolic steatohepatitis, leads to a high incidence and prevalence of this neoplasia worldwide. Despite the spread of HCC, its treatment it's still a hard challenge, due to high rate of late diagnosis and to lack of therapeutic options for advanced disease. In fact radical surgery and liver transplantation, the most radical therapeutic approaches, are indicated only in case of early diagnosis. Even local therapies, such as transarterial chemoembolization, find limited indications, leading to an important problem regarding treatment of advanced disease. In this situation, until terminal HCC occurs, systemic therapy is the only possible approach, with sorafenib as the only standard treatment available. Anyway, the efficacy of this drug is limited and many efforts are necessary to understand who could benefit more with this treatment. Therefore, other molecules for a targeted therapy were evaluated, but only regorafenib showed promising results. Beside molecular target therapy, also cytotoxic drugs, in particular oxaliplatinand gemcitabine-based regimens, and immune-checkpoint inhibitors were tested with interesting results. The future of the treatment of this neoplasia is linked to our ability to understand its mechanisms of resistance and to find novel therapeutic targets, with the objective to purpose individualized approaches to patients affected by advanced HCC.

Combinational adenovirus-mediated gene therapy and dendritic cell vaccine in combating well-established tumors

Recent developments in tumor immunology and biotechnology have made cancer gene therapy and immunotherapy feasible. The current efforts for cancer gene therapy mainly focus on using immunogenes, chemogenes and tumor suppressor genes. Central to all these therapies is the development of efficient vectors for gene therapy. By far, adenovirus （AdV）-mediated gene therapy is one of the most promising approaches, as has confirmed by studies relating to animal tumor models and clinical trials. Dendritic cells （DCs） are highly efficient, specialized antigen-presenting cells, and DC- based tumor vaccines are regarded as having much potential in cancer immunotherapy. Vaccination with DCs pulsed with tumor peptides, lysates, or RNA, or loaded with apoptotic/necrotic tumor cells, or engineered to express certain cytokines or chemokines could induce significant antitumor cytotoxic T lymphocyte （CTL） responses and antitumor immunity. Although both AdV-mediated gene therapy and DC vaccine can both stimulate antitumor immune responses, their therapeutic efficiency has been limited to generation of prophylactic antitumor immunity against re-challenge with the parental tumor cells or to growth inhibition of small tumors. However, this approach has been unsuccessful in combating well-established tumors in animal models. Therefore, a major strategic goal of current cancer immunotherapy has become the development of novel therapeutic strategies that can combat well-established tumors, thus resembling real clinical practice since a good proportion of cancer patients generally present with significant disease. In this paper, we review the recent progress in AdV-mediated cancer gene therapy and DC-based cancer vaccines, and discuss combined immunotherapy including gene therapy and DC vaccines. We underscore the fact that combined therapy may have some advantages in combating well-established tumors vis-a-vis either modality administered as a monotherapy.

Prognostic and predictive biomarkers in metastatic colorectal cancer anti-EGFR therapy

AIM: To reviewing genetic and epigenetic make-up of metastatic colorectal cancers (mCRCs) addicted to epidermal growth factor receptor (EGFR) signalling.METHODS: The present study summarizes the potential value of prognostic and predictive biomarkers in selecting mCRC patients treated with anti-EGFR therapy. A meta-analysis was performed using a systematic search of PubMed, Medline and Web of Science to identify eligible papers until March 21st, 2016 using these following terms: ‘‘colorectal cancer’’, “predictive biomarkers’’, “anti-EGFR therapy”, “KRAS”, “NRAS’’, “PIK3CA”, “TP53”, “PTEN”, ‘‘EGFR”, “MET”, “HER2”, “epiregulin”, “amphiregulin”, “prognostic biomarkers”, “BRAF”, “miRNA” and “antibody-dependent cell-mediated cytotoxicity (ADCC) activity”. Two investigators independently evaluated and extracted data from each identified studies based on selected criteria of inclusion and exclusion.RESULTS: The introduction of agents targeting EGFR such as cetuximab and panitumumab increased overall survival of mCRCs. Nevertheless, it has firstly became evident that response rates to cetuximab regimens in unselected patient populations were typically lower than 30%. Clinical data confirmed the predictive value of RAS mutations for resistance to cetuximab and panitumumab leading to the license of these monoclonal antibodies exclusively for the management of patients with RAS-wild type colorectal cancers. So far the identification of predictive biomarkers have generated interesting, though preliminary and, at times, conflicting data on the importance of tumour mRNA levels of EGFR ligands, of activating mutations in other genes such as NRAS and PIK3CA. The prognostic value of selected microRNAs level and ADCC activity is under investigation, while the prognostic impact of BRAF status remains controversial.CONCLUSION: This review focuses on the personalized treatment of mCRC and discusses the potential of new prognostic and predictive biomarkers in selecting patients treated with anti-EGFR therapy.

Immunotherapy in pancreatic cancer:Unleash its potential through novel combinations

Pancreatic cancer is the third leading cause of cancer mortality in both men and women in the United States,with poor response to current standard of care,short progression-free and overall survival.Immunotherapies that target cytotoxic T lymphocyte antigen-4,programmed cell death protein-1,and programmed death-ligand 1 checkpoints have shown remarkable activities in several cancers such as melanoma,renal cell carcinoma,and nonsmall cell lung cancer due to high numbers of somatic mutations,combined with cytotoxic T-cell responses.However,single checkpoint blockade was ineffective in pancreatic cancer,highlighting the challenges including the poor antigenicity,a dense desmoplastic stroma,and a largely immunosuppressive microenvironment.In this review,we will summarize available clinical results and ongoing efforts of combining immune checkpoint therapies with other treatment modalities such as chemotherapy,radiotherapy,and targeted therapy.These combination therapies hold promise in unleashing the potential of immunotherapy in pancreatic cancer to achieve better and more durable clinical responses by enhancing cytotoxic T-cell responses.

细胞毒治疗相关髓系肿瘤患者的临床特征及实验室结果分析

目的分析细胞毒治疗相关髓系肿瘤(MN-pCT)患者的临床特征及实验室结果,以提高对该类疾病的认识,协助临床诊疗。方法回顾性分析2011年1月至2022年6月该院诊断为MN-pCT患者22例的临床特征及相关实验室结果,其中细胞毒治疗相关急性髓系白血病(AML-pCT)16例,细胞毒治疗相关骨髓增生异常综合征(MDS-pCT)5例,细胞毒治疗相关骨髓增生异常综合征/骨髓增殖性肿瘤(MDS/MPN-pCT)1例。结果22例MN-pCT患者中,原发疾病以恶性肿瘤为主19例(86.36%),其次为自身免疫性疾病3例(13.64%)。不同年龄、原发疾病、治疗方式、染色体核型及血常规降低情况患者的潜伏期比较,差异均无统计学意义(P>0.05)。AML-pCT不同预后情况患者间性别、年龄、血红蛋白水平、中性分叶核粒细胞计数、血小板计数、乳酸脱氢酶(LDH)水平、外周血原始细胞比例及潜伏期比较,差异无统计学意义(P>0.05);AML-pCT组患者的骨髓原始细胞比例及LDH水平高于MDS-pCT组(P<0.05),而两组患者其余临床资料及实验室检查结果比较,差异无统计学意义(P>0.05)。结论MN-pCT患者病死率高、预后差,综合实验室检查与临床特征有助于及时发现并诊治MN-pCT,改善患者预后。

Type 1 CD8^+ T Cells are Superior to Type 2 CD8^+ T Cells in Tumor Immunotherapy due to Their Efficient Cytotoxicity,Prolonged Survival and Type 1 Immune Modulation

CD8^＋ cytotoxic T （Tc） cells play a crucial role in host immune responses to cancer, and in this context, adoptive CD8^＋ Tc cell therapy has been studied in numerous animal tumor models. Its antitumor efficacy is, to a large extent, determined by the ability of Tc cells to survive and infiltrate tumors. In clinical trials, such in vitro-activated T cells often die within hours to days, and this greatly limits their therapeutic efficacy. CD8^＋ Tc cells fall into two subpopulations based upon their differential cytokine secretion. In this study, we in vitro generated that ovalbumin （OVA）-pulsed dendritic cell （DCovA）-activated CD8^＋ type 1 Tc （Tcl） cells secreting IFN-T, and CD8^＋ type 2 Tc （Tc2） cells secreting IL-4, IL-5 and IL-10, which were derived from OVA-specific T cell receptor （TCR） transgenic OT I mice. We then systemically investigated the in vitro and in vivo effector function and survival of Tcl and Tc2 cells, and then assessed their survival kinetics after adoptively transferred into C57BL/6 mice, respectively. We demonstrated that, when compared to CD8^＋ Tc2, Tcl cells were significantly more effective in perforin-mediated cytotoxicity to tumor cells, had a significantly higher capacity for in vivo survival after the adoptive T cell transfer, and had a significantly stronger therapeutic effect on eradication of well-established tumors expressing OVA in animal models. In addition, CD8^＋ Tcl and Tc2 cells skewed the phenotype of CD4^＋ T cells toward Thl and Th2 type, respectively. Therefore, the information regarding the differential effector function, survival and immune modulation of CD8^＋ Tcl and Tc2 cells may provide useful information when preparing in vitro DC-activated CD8^＋ T cells for adoptive T cell therapy of cancer.

融合PE38的抗CD70纳米抗体免疫毒素的制备及其对肾透明细胞癌786-O细胞的杀伤作用

目的:构建靶向CD70分子的重组免疫毒素,通过表达、纯化制备PE38与抗CD70纳米抗体重组蛋白,体外抗肿瘤实验探究重组蛋白是否对高表达CD70分子的阳性肿瘤细胞具有杀伤活性。方法:通过基因工程手段,将CD70纳米抗体Nb 2B3基因片段通过一个连接子与pET21a-PE38基因片段相连,获得重组表达载体pET21a-Nb 2B3-PE38并转入BL21(DE3)感受态细胞中进行表达、纯化与鉴定。用间接ELISA及FACS法检测Nb 2B3-PE38与CD70分子的结合活性,MTT法检测Nb 2B3-PE38对高表达CD70分子的肾透明细胞癌786-O细胞的体外杀伤活性,AnnexinⅤ-FITC/PI双染法检测Nb 2B3-PE38对786-O细胞凋亡的影响。结果:成功构建抗CD70纳米抗体重组免疫毒素Nb 2B3-PE38,纯化获得纯度>90%的重组蛋白,SDS-PAGE及WB检测结果表明目的蛋白正确表达,分子量为56000。纯化后的Nb 2B3-PE38能与重组CD70抗原及786-O细胞表面的CD70分子特异性结合;25μg/mL Nb 2B3-PE38即对786-O细胞产生极显著的杀伤作用(P<0.001),并且促进786-O细胞的细胞凋亡(P<0.01),其杀伤效应强于阳性对照顺铂(P<0.01)。结论:成功制备了特异性靶向CD70分子的免疫毒素Nb 2B3-PE38,其能够有效杀伤786-O细胞并诱导细胞凋亡且效果强于顺铂。

聚多巴胺并木犀草素对细胞毒性淋巴细胞肿瘤杀伤作用的影响

目的 探讨聚多巴胺(PDA)并木犀草素(LUT)通过光热治疗对细胞毒性淋巴细胞(CTL)肿瘤杀伤作用的影响。方法 通过扫描电子显微镜(SEM)和接触角测定仪观察和测定合成PDA的表征。将RAW264.7细胞分为Control组、LPS组(2μg/L)、PDA′组(50 000μg/L),常规培养48 h,采用CCK8实验检测细胞活力,通过流式细胞术检测LUT对RAW264.7细胞分化的影响。将雌性C57BL/6小鼠随机分为模型组、PDA组、LUT组以及PDA+LUT组,各组小鼠的后背部均皮下注射B16F10黑色素瘤细胞,建模后第10天在PDA组和PDA+LUT组建模小鼠肿瘤处注射PDA行光热治疗1次后,对建模小鼠右大腿肌肉分别注射PBS、PDA(2.5μg/只)、LUT(500μg/只)、PDA(2.5μg/只)+LUT(500μg/只),观察建模小鼠肿瘤生长以及存活情况。在治疗后第3、7天,取各组建模小鼠脾脏制备单细胞悬液,采用流式细胞术检测小鼠体内巨噬细胞分化和T细胞表达情况。结果SEM观察到合成的PDA具有较强的吸附能力和亲水性,并且CCK8实验检测结果显示PDA对细胞活力无影响(P>0.05)。各组RAW264.7细胞的CD206和iNOS平均荧光强度差异有显著性(F=30.72、1 516.00,P<0.05)。注射或不注射PDA时,则注射或不注射LUT小鼠的肿瘤大小和体内免疫细胞iNOS、CD206、IFN-γ^(+)CD4^(+)、TNF-α^(+)CD8^(+)表达水平比较差异均有显著性(F=23.10~235.52,P<0.05);注射或不注射LUT时,则注射或不注射PDA小鼠的肿瘤大小和体内免疫细胞iNOS、CD206、CD4^(+)IFN-γ^(+)、CD8^(+)TNF-α^(+)表达水平比较差异均有显著性(F=8.98~200.67,P<0.05);建模小鼠中PDA+LUT组存活率与其他组相比显著提高(χ^(2)=9.70,P<0.01)。结论 LUT具有抑制小鼠巨噬细胞向M2分化并促进其向M1分化的作用,PDA并LUT治疗可以有效抑制小鼠肿瘤生长,提高生存率,增强CTL的肿瘤杀伤作用。

从基础研究到临床实践:调节性T细胞在移植免疫耐受中的应用研究进展

调节性T细胞(Treg)是机体建立免疫耐受的重要抑制性免疫细胞,在调控机体过度免疫应答和自身免疫性疾病中发挥着重要作用。在移植免疫耐受相关研究中,增加体内Treg数量或增强其功能已被证明是一种能够诱导移植免疫耐受的治疗策略。目前,基于Treg诱导移植免疫耐受的方法包括过继输注Treg、体内扩增Treg和利用抗原特异性Treg。本文对Treg的特征及其作用机制,基础实验最新研究进展及国内外与移植免疫耐受相关的Treg临床实践进行综述,并对Treg治疗未来的挑战与发展进行展望,旨在揭示Treg在移植免疫耐受相关研究中的重要性和应用前景,探讨Treg治疗策略的优势和局限性,并为今后该领域的研究提供参考依据和启示。

富勒烯的生物活性研究进展

９０年代初以来，富勒烯类化合物的生物活性逐渐引起人们的注意，初步研究表明在抗艾滋病毒、酶活性抑制、切割ＤＮＡ、光动力学治疗等方面具有独特的功效．此类化合物在生化、医学、药物学等领域有良好的应用前景．

CTLA4Ig重组腺病毒载体的构建与体外表达

目的 :构建含有CTLA4Ig基因的重组腺病毒载体 ,为下一步在动物模型体内表达和基因治疗提供基础。方法 :自行设计一对分别含有BglⅡ及HindⅢ酶切位点的CTLA4Ig基因上下游引物 ,以质粒PCDNA3 0 /CTLA4Ig为模板 ,通过PCR扩增获得CTLA4Ig基因全部序列。片段回收以后经BglⅡ及HindⅢ双酶切 ,定向插入到腺病毒穿梭质粒pAdTrack -CMV的启动子下游BglⅡ及HindⅢ位点之间 ,获得重组质粒pAdTrack -CTLA4Ig。通过BglⅡ /HindⅢ双酶切、PCR及插入片段测序鉴定后 ,将正确重组体pAdTrack -CTLA4Ig与腺病毒骨架质粒pAdEasy - 1共转化BJ5 183细菌。同源重组后用选择性培养基筛选阳性克隆 ,提取质粒用脂质体介导转染 2 93细胞 ,通过观察绿色荧光蛋白(GFP)的表达及PCR扩增目的基因等方法鉴定重组的腺病毒。结果 :成功构建了含有CTLA4Ig基因的重组腺病毒 ,病毒滴度为 1 6 5× 10 12 PFU/L。结论 :该重组腺病毒的构建为下一步研究其在哺乳动物细胞内表达、研究CTLA4Ig的生物学活性及移植排斥、自身免疫病的基因治疗提供了一定的基础。

LDH释放法检测肿瘤患者PBMC和CIK细胞的细胞毒活性

目的建立检测细胞毒活性的乳酸脱氢酶(LDH)测定法,了解肿瘤患者外周血单个核细胞(PBMC)和细胞因子诱导的杀伤细胞(CIK)的抗肿瘤活性,为肿瘤的免疫细胞治疗提供参考。方法采集肿瘤患者和健康成人外周血,常规分离PBMC,体外进行CIK的培养,用LDH释放法分别检测PBMC和CIK对肿瘤细胞K562的细胞毒活性。结果肿瘤患者PBMC对K562的杀伤活力比正常人显著降低(P<0.05)。经多种细胞因子诱导培养7～10d后,健康人和肿瘤患者的CIK对K562的杀伤活力都有显著提高(P<0.01),肿瘤患者CIK杀伤活力接近于健康人。结论肿瘤患者PBMC细胞毒活性显著降低,但经诱导培养成CIK后则显著提高。用LDH释放法检测肿瘤病人CIK细胞毒活力,有助于CIK疗法适应病人的选择及个体疗效观察。

靶向抗肿瘤抗体-药物偶联物研究进展

靶向治疗已成为当今肿瘤研究领域的热点。抗体-药物偶联物(antibody drug conjugates,ADC)兼具抗体的高特异性和细胞毒药物对肿瘤的高毒性,代表了新一代抗体技术的发展方向。ADC由"弹头"药物(细胞毒药物)、抗体以及偶联抗体和药物的偶联链3部分组成。ADC利用抗体作为载体将"弹头"药物送至靶部位,并通过细胞内吞效应进入溶酶体,释放出细胞毒性药物,从而达到专一性杀死癌细胞而不损伤正常组织细胞的作用。本文综述近年来ADC研制和发展趋势,并探讨ADC研发过程中的几个可能的关键影响因素。