肿瘤过继性细胞免疫治疗进展

过继性细胞免疫治疗(ACI)是肿瘤治疗的重要手段,通过回输体外扩增及激活的肿瘤特异性免疫细胞,达到控制肿瘤的目的.虽然ACI在恶性黑色素瘤的治疗中取得了可喜的疗效,但患者完全缓解率仍不足10％,而且ACI对其他肿瘤的临床疗效欠佳.近年来研究表明,改善细胞培养方法、优化成分组成、增强细胞本身功能以及联合其他治疗等是进一步提高肿瘤细胞免疫治疗的关键.     

肿瘤过继性细胞治疗的研究进展

肿瘤因其发病机理不明确,患病致死率高,治疗极其困难。目前传统治疗方法有手术切除、放射治疗、化学药物治疗三大模式,传统治疗方法均存在毒副作用大,药物作用靶点不清晰,肿瘤易复发等缺陷。肿瘤过继性细胞治疗是基于肿瘤患者自身免疫细胞开发的一种新型治疗,本文对肿瘤过继性细胞治疗方案进行探讨,重点对嵌和抗原受体细胞疗法进行分析,归纳总结肿瘤过继性细胞治疗的研究进展。     

T细胞过继免疫治疗恶性实体肿瘤研究进展

过继细胞免疫治疗（adoptive cellular immunotherapy，ACI）在血液系统疾病的临床应用已获得广泛认可，尤其在目前疫苗免疫治疗还存在着不能有效抑制微小残留肿瘤生长等多种因素而限制了其临床应用的前提下，ACI在恶性实体肿瘤治疗中的应用研究也引起了人们的普遍关注。     

自体CD3AK细胞过继免疫治疗晚期恶性肿瘤的临床观察

目的观察抗CD3单克隆抗体（anti—CD3 mAb）激活的杀伤细胞（cD3AK）过继免疫治疗晚期恶性肿瘤的疗效。方法从51例恶性肿瘤患者自体外周血分离单个核细胞,加入anti—CD3mAb、重组人IL-2（rhIL-2）体外诱导后扩增培养,制备自体CD3AK细胞。待细胞培养至第10～12天时取样用于质控检测。收集质控检测合格的CD3AK细胞,调整至终浓度为（4．0～6．0）×10^9/L,静脉回输至患者体内,每例患者治疗3个疗程,每疗程回输5次（每2d回输1次）,每次回输细胞数不低于1×10^9,每疗程回输细胞总数大于5×10^＊。应用人T细胞亚群检测试剂盒和流式细胞仪测定治疗前后患者外周血CD3＋、CD4＋、CD8＋T细胞以及CD16＋56＋细胞（NK细胞）比例;观察治疗前后患者的相关化验指标、生活质量以及不良反应;评定疗效,计算有效率和临床受益率。结果分离制备的CD3AK细胞符合理想活性细胞质量要求,可用于进一步实验治疗。CD3AK细胞过继免疫治疗后,患者外周血CD3＋、CD4＋、CD8＋T细胞以及CD16＋56＋细胞（NK细胞）比例分别为（48．88±9．42）％、（35．09±4．11）％、（28．17±4．97）％、（20.31±6．98）％]均显著升高（均P〈0．05）。51例患者中,45例患者治疗后全身症状改善明显;所有患者治疗后相关化验指标均未出现异常变化,也未出现其他全身毒副反应;其中完全缓解6例、部分缓解14例、微效11例、稳定12例、进展8例,总有效率达60．8％,临床受益率达84．3％。结论CD3AK细胞过继免疫治疗恶性肿瘤疗效确切、安全且无副作用,能有效改善和提高患者的机体免疫功能。     

癌症疼痛的治疗进展

癌症是当今严重威胁人类健康和生命的疾病之一。解除癌症疼痛对改善患者的生活质量非常有意义,了解癌性疼痛的发生机制和治疗方法对治好癌症疼痛起着基础作用。本文就癌痛的发生机制,癌痛治疗的方法和药物进行阐述。     

癌症疼痛的治疗进展

癌症是当今严重威胁人类健康和生命的疾病之一.解除癌症疼痛对改善患者的生活质量非常有意义,了解癌性疼痛的发生机制和治疗方法对治好癌症疼痛起着基础作用.本文就癌痛的发生机制,癌痛治疗的方法和药物进行阐述.     

γδT细胞过继细胞免疫治疗恶性实体肿瘤研究进展

近年来对恶性实体瘤的治疗效果有了显著提高,但发生复发和转移的比例仍较高。免疫治疗是恶性肿瘤治疗的有效方法之一,其中过继免疫细胞治疗是目前研究的热点。与需要抗原提呈并具有主要组织相容性复合体(MHC)限制性的αβT细胞不同,γδT细胞对肿瘤细胞的识别、杀伤显现出MHC非限制性,因此γδT细胞作为种子细胞的过继免疫治疗得到了人们的关注。目前已证实γδT细胞针对多种恶性实体瘤具有杀伤作用,尤其重要的是临床验证了γδT细胞对部分恶性实体瘤的有效性。本文综述了γδT细胞的分型、作用机制和应用现状,重要的是,讨论了γδT细胞联合双磷酸盐、基因调整的αβTCR转染γδT细胞治疗恶性实体瘤的可能策略。     

临床证实质子治疗适用于肺癌、肝癌等常见癌症

据报道，质子技术是目前世界上肿瘤放射线治疗领域的最先进技术，该技术对人体健康细胞的损害小，对于治疗有重要组织器官包绕的肿瘤尤有明显优势。     

T细胞受体基因转染过继性免疫治疗的研究进展

利用T细胞进行过继性免疫治疗是治疗病毒感染性疾病和肿瘤的理想方法,但是用于治疗的T细胞的特异性、亲和性和数量等限制了其应用,如何获得特异、高效、一定数量的T细胞是目前亟待解决的问题。采用TCR基因转染的方法,将特异性高亲和力TCR转移到受体的T细胞中,可以特异性杀伤受体体内的肿瘤细胞。     

研究表明：细菌蛋白可对抗癌症细胞

以细菌治疗癌症的疗法可追溯到一百年前,不过这些疗法虽然有时真的能让肿瘤缩小,但却往往会在疗程中产生毒素,而限制了它在医疗上的应用价值.最近美国伊利诺州大学研究人员把细菌中具有疗效的蛋白分离出来,而研究结果也显示用这个蛋白治疗癌症,并不会出现严重的副作用.这个有可能成为对抗癌症的新武器azurin蛋白,是从绿脓杆菌中分离出来的.这种细菌常常对抗生素有抗药性,而且会造成人类严重的呼吸道     

Mesothelin-targeted CAR-T cells for adoptive cell therapy of solid tumors

Significant progresses have been made in adoptive cell therapy with CAR-T cells for cancers, especially for hematological malignancies. However, the treatment of solid tumors still poses a tremendous challenge and remains an unmet medical need. Several factors are held responsible for the inadequate responses: tumor heterogeneity, inefficient homing of T cells to tumor tissues, immunosuppressive microenvironment and the shortage of specific antigens shortage. Mesothelin is a cell-surface glycoprotein highly expressed in many types of solid tumors. As such, it has attracted much attention as a molecular target in cancer immunotherapy. Here, we delineate the barriers imposed by solid tumors on CARs, outline the rationale of mesothelin as a target for immunotherapy, summarize the preclinical and clinical results of mesothelin-targeted therapies, and extrapolate the expected results of CAR-T cells directed against mesothelin for solid tumors.     

Exploiting the curative potential of adoptive T-cell therapy for cancer

Adoptive T-cell therapy (ACT) is a potent and flexible cancer treatment modality that can induce complete, durable regression of certain human malignancies. Long-term follow-up of patients receiving tumor-infiltrating lymphocytes (TILs) for metastatic melanoma reveals a substantial subset that experienced complete, lasting tumor regression – and may be cured. Increasing evidence points to mutated gene products as the primary immunological targets of TILs from melanomas. Recent technological advances permit rapid identification of the neoepitopes resulting from these somatic gene mutations and of T cells with reactivity against these targets. Isolation and adoptive transfer of these T cells may improve TIL therapy for melanoma and permit its broader application to non-melanoma tumors. Extension of ACT to other malignancies may also be possible through antigen receptor gene engineering. Tumor regression has been observed following transfer of T cells engineered to express chimeric antigen receptors against CD19 in B-cell malignancies or a T-cell receptor against NY-ESO-1 in synovial cell sarcoma and melanoma. Herein, we review recent clinical trials of TILs and antigen receptor gene therapy for advanced cancers. We discuss lessons from this experience and consider how they might be applied to realize the full curative potential of ACT.     

Harnessing innate and adaptive immunity for adoptive cell therapy of renal cell carcinoma

The development of immunotherapies for renal cell carcinoma (RCC) has been the subject of research for several decades. In addition to cytokine therapy, the benefit of various adoptive cell therapies has again come into focus in the past several years. Nevertheless, success in fighting this immunogenic tumor is still disappointing. RCC can attract a multitude of different effector cells of both the innate and adaptive immune system, including natural killer (NK) cells, γδ T cells, NK-like T cells, peptide-specific T cells, dendritic cells (DC), and regulatory T cells (Tregs). Based on intensive research on the biology and function of different immune cells, we now understand that individual cell types do not act in isolation but function within a complex network of intercellular interactions. These interactions play a pivotal role in the efficient activation and function of effector cells, which is a prerequisite for successful tumor elimination. This review provides a current overview of the diversity of effector cells having the capacity to recognize RCC. Aspects of the functions and anti-tumor properties that make them attractive candidates for adoptive cell therapies, as well as experience in clinical application are discussed. Improved knowledge of the biology of this immune network may help us to effectively harness various effector cells, placing us in a better position to develop new therapeutic strategies to successfully fight RCC.     

Immunotherapy of cancer employing adoptiveT cell transfer

Adoptive T cell immunotherapy of cancer involvespassive administration of lymphoid cells from onehost to another, or back to itself in order to trans fer tumor immunity for cancer treatment. It wasfirst realized more than twenty years ago that adop tive immunotherapy may be feasible to treat humanmalignancies. However, the early form of thispractice was quite simple. It could be as easy as astraightforward blood cell transfer. The apparentinefficiency of antitumor immune respon…     

Progression of antibody therapy in the cancer therapy anti-CCR4 antibody and others

Recently, a lot of new anti-cancer agents have come to the cancer treatment scene. The development of monoclonal antibodies like rituximab, trastuzumab, cetuximab, and bevacizumab are symbolic of the new era, and their effect on the various cancers is remarkable. They have occupied essential position in the cancer treatment as a first-line therapy or as an adjuvant therapy. In Japan, the approval of drugs which are not only anti-cancer agent but also any other drugs don't have been quick for long ago. So when we treat the cancer patient with their new agent, there is the limitation in the way to use them. But we should not only submit to this situation, as a member of worker in Japanese medical academic, clinical, industrial situation should progress the research and development and clinical study of the new anti-cancer agent including monoclonal antibody.     

Engineering of chimeric natural killer cell receptors to develop precision adoptive immunotherapies for cancer

Natural killer (NK) cells are innate immune effectors which play a crucial role in recognizing and eliminating virally infected and cancerous cells. They effectively distinguish between healthy and distressed self through the integration of signals delivered by germline-encoded activating and inhibitory cell surface receptors. The frequent up-regulation of stress markers on genetically unstable cancer cells has prompted the development of novel immunotherapies that exploit such innate receptors. One prominent example entails the development of chimeric antigen receptors (CAR) that detect cell surface ligands bound by NK receptors, coupling this engagement to the delivery of tailored immune activating signals. Here, we review strategies to engineer CARs in which specificity is conferred by natural killer group 2D (NKG2D) or other NK receptor types. Multiple preclinical studies have demonstrated the remarkable ability of chimeric NK receptor-targeted T cells and NK cells to effectively and specifically eliminate cancer cells and to reject established tumour burdens. Importantly, such systems act not only acutely but, in some cases, they also incite immunological memory. Moreover, CARs targeted with the NKG2D ligand binding domain have also been shown to disrupt the tumour microenvironment, through the targeting of suppressive T regulatory cells, myeloid-derived suppressor cells and tumour vasculature. Collectively, these findings have led to the initiation of early-phase clinical trials evaluating both autologous and allogeneic NKG2D-targeted CAR T cells in the haematological and solid tumour settings.     

神经干细胞与癫痫治疗研究进展

癫痫是一种常见的神经系统疾病，其发病机制极为复杂。近年来，国内外在神经干细胞移植治疗癫痫方面作了大量的试验研究。神经干细胞移植入癫痫脑后可引起形态学、电生理、临床疗效的改变，并影响所涉及的神经递质和信号转导机制，为神经干细胞移植治疗癫痫的可行性提供了依据。