Chimeric antigen receptor-engineered T-cell therapy for liver cancer

Background: Chimeric antigen receptor-engineered T-cell(CAR-T) therapy is a newly developed immunotherapy used in the treatment of cancers. Because CAR-T therapy has shown great success in treating CD19-positive hematological malignancies, its application has been explored in the treatment of solid tumors, such as liver cancer. In this review, we discuss the immune characteristics of liver cancer, the obstacles encountered during the application of CAR-T therapy, and preclinical and clinical progress in the use of CAR-T therapy in patients with liver cancer.Data sources: The data on CAR-T therapy related to liver cancers were collected by searching Pub Med and the Web of Science databases prior to December 2017 with the keywords "chimeric antigen receptor","CAR-T", "liver cancer", "hepatocellular carcinoma", and "solid tumor". Additional articles were identified by manual search of references found in the primary articles. The data for clinical trials were collected by searching Clinical Trials.gov.Results: The liver has a tolerogenic nature in the intrahepatic milieu and its tumor microenvironment significantly affects tumor progression. The obstacles that reduce the efficacy of CAR-T therapy in solid tumors include a lack of specific tumor antigens, limited trafficking and penetration of CAR-T cells to tumor sites, and an immunosuppressive tumor microenvironment. To overcome these obstacles, several strategies have emerged. In addition, several strategies have been developed to manage the side effects of CAR-T, including enhancing the selectivity of CARs and controlling CAR-T activity. To date, no clinical trials of CAR-T therapy against HCC have been completed. However, preclinical studies in vitro and in vivo have shown potent antitumor efficacy. Glypican-3, mucin-1, epithelial cell adhesion molecule, carcinoembryonic antigen, and other targets are currently being studied.Conclusions: The application of CAR-T therapy for liver cancer is just beginning to be explored and more research is needed. However, we are optimistic that CAR-T therapy will offer a new approach for the treatment of liver cancers in the future.

Chimeric antigen receptors:On the road to realising their full potential

Chimeric antigen receptors （CARs） are fusion molecules that may be genetically delivered ex-vivo to T-cells and other immune cell populations, thereby conferring specifcity for native target antigens found on the surface of tumour and other target cell types. Antigen recognition by CARs is neither restricted by nor dependent upon human leukocyte antigen antigen expression, favouring widespread use of this technology across transplantation barriers. Signalling is delivered by a designer endodomain that provides a tailored and target-dependent activation signal to polyclonal circulating T-cells. Recent clinical data emphasise the enormous promise of this emer-ging immunotherapeutic strategy for B-cell malignancy, notably acute lymphoblastic leukaemia. In that context, CARs are generally targeted against the ubiquitous B-cell antigen, CD19. However, CAR T-cell immunotherapy is limited by potential for severe ontarget toxicity, notably due to cytokine release syndrome. Furthermore, effcacy in the context of solid tumours remains unproven, owing in part to lack of availability of safe tumourspecific targets, inadequate CAR T-cell homing and hostility of the tumour microenvironment to immune effector deployment. Manufacture and commercial development encountered with more traditional drug products. Finally, there is increasing interest in the application of this technology to the treatment of non-malignant disease states, such as autoimmunity, chronic infection and in the suppression of allograft rejection. Here, we consider the background and direction of travel of this emerging and highly promising treatment for malignant and other disease types.

Donor-derived CD 19 CAR-T Cells versus Chemotherapy Plus Donor Lymphocyte Infusion for Treatment of Recurrent CD 19-positive B-ALL after Allogeneic Hematopoietic Stem Cell Transplantation

Objective:This study aimed to compare the efficacy of anti-CD19 chimeric antigen receptor T cells(CAR-T cells)versus chemotherapy plus donor lymphocyte infusion(chemo-DLI)for treating relapsed CD 19-positive B-cell acute lymphoblastic leukemia(B-ALL)after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods:Clinical data of 43 patients with B-ALL who relapsed after allo-HSCT were retrospectively analyzed.Twenty-two patients were treated with CAR-T cells(CAR-T group),and 21 with chemotherapy plus DLI(chemo-DLI group).The complete remission(CR)and minimal residual disease(MRD)-negative CR rates,leukemia-free survival(LFS)rate,overall survival(OS)rate,and incidence of acute graft-versus-host disease(aGVHD),cytokine release syndrome(CRS)and immune effector cell-associated neurotoxicity syndrome(ICANS)were compared between the two groups.Results:The CR and MRD-negative CR rates in the CAR-T group(77.3%and 61.5%)were significantly higher than those in the chemo-DLI group(38.1%and 23.8%)(P=0.008 and P=0.003).The 1-and 2-year LFS rates in the CAR-T group were superior to those in the chemo-DLI group:54.5%and 50.0%vs.9.5%and 4.8%(P=0.0001 and P=0.00004).The 1-and 2-year OS rates in the CAR-T versus chemo-DLI group were 59.1%and 54.5%vs.19%and 9.5%(P=0.011 and P=0.003).Six patients(28.6%)with grade 2-4 aGVHD were identified in the chemo-DLI group.Two patients(9.1%)in the CAR-T group developed grade 1-2 aGVHD.Nineteen patients(86.4%)developed CRS in the CAR-T group,comprising grade 1-2 CRS in 13 patients(59.1%)and grade 3 CRS in 6 patients(27.3%).Two patients(9.1%)developed grade 1-2 ICANS.Conclusion:Donor-derived anti-CD19 CAR-T-cell therapy may be better,safer,and more effective than chemo-DLI for B-ALL patients who relapse after allo-HSCT.

Revolutionizing gastric cancer treatment:The potential of immunotherapy

Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk factors include family medical history,dietary habits,tobacco use,Helicobacter pylori,and Epstein-Barr virus infections.Unfortunately,gastric cancer is often diagnosed at an advanced stage,leading to a grim prognosis,with a 5-year overall survival rate below 5%.Surgical intervention,particularly with D2 Lymphadenectomy,is the mainstay for early-stage cases but offers limited success.For advanced cases,the National Comprehensive Cancer Network recommends chemotherapy,radiation,and targeted therapy.Emerging immunotherapy presents promise,especially for unresectable or metastatic cases,with strategies like immune checkpoint inhibitors,tumor vaccines,adoptive immunotherapy,and nonspecific immunomodulators.In this Editorial,with regards to the article“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review”,we address the advances in the field of immunotherapy in gastric cancer and its future prospects.

Engineered T Cell Therapies from a Drug Development Viewpoint

Cancer is one of the leading causes of death worldwide. Recent advances in cellular therapy have demonstrated that this platform has the potential to give patients with certain cancers a second chance at life. Unlike chemical compounds and proteins, cells are living, self-replicating drugs that can be engineered to possess exquisite specificity. For example, T cells can be genetically modified to express chimeric antigen receptors (CARs), endowing them with the capacity to recognize and kill tumor cells and form a memory pool that is ready to strike back against persisting malignant cells. Anti-CD19 chimeric antigen receptor T cells (CART19s) have demonstrated a remarkable degree of clinical efficacy for certain malignancies. The process of developing CART19 essentially follows the conventional “one gene, one drug, one disease” paradigm derived from Paul Ehrlich’s “magic bullet” concept. With major players within the pharmaceutical industry joining forces to commercialize this new category of “living drugs,” it is useful to use CART19 as an example to examine the similarities and differences in its development, compared with that of a conventional drug. In this way, we can assimilate existing knowledge and identify the most effective approach for advancing similar strategies. This article reviews the use of biomarker-based assays to guide the optimization of CAR constructs, preclinical studies, and the evaluation of clinical efficacy;adverse effects (AEs);and CART19 cellular kinetics. Advanced technologies and computational tools that enable the discovery of optimal targets, novel CAR binding domains, and biomarkers predicting clinical response and AEs are also discussed. We believe that the success of CART19 will lead to the development of other engineered T cell therapies in the same manner that the discovery of arsphenamine initiated the era of synthetic pharmaceuticals.

过继性T细胞疗法在头颈部鳞癌中的研究进展

过继性T细胞疗法(adoptive T cell therapy,ACT)是一种高度个性化的抗肿瘤治疗方法,临床研究正在迅速发展。研究表明,ACT疗法可以通过增加T细胞数量,增强对肿瘤组织的特异性和反应性,从而克服肿瘤免疫缺陷抑制的产生。ACT疗法目前有3种主要模式:肿瘤浸润淋巴细胞(TILs)、嵌合抗原受体T细胞(CAR-T)和T细胞受体工程化T细胞(TCR-T)治疗。本文对ACT疗法的分类及研究进展进行综述,包括TILs、CAR-T、TCR-T以及基于类器官共培养的过继性T淋巴细胞免疫治疗,探讨ACT作为头颈部鳞癌治疗方式的应用前景。

CD22CAR-T挽救治疗CD19CAR-T治疗后短期复发的TP53突变阳性难治急性B淋巴细胞白血病一例

难治急性淋巴细胞白血病病死率极高,CAR-T细胞免疫治疗为此提供新的选择。本文介绍1例CD19 CAR-T细胞治疗缓解后短期复发的TP53突变阳性难治急性B淋巴细胞白血病,经CD22CAR-T联合单倍体异基因造血干细胞移植治疗成功的病例。本研究采用流式细胞术观察患者CD19CAR-T细胞和CD22CAR-T细胞两次治疗的外周血CAR-T细胞比例,PCR法检测CAR基因表达;临床观察患者2次CAR-T细胞治疗过程中的疗效和不良反应。结果显示,CD19CAR-T和CD22CAR-T细胞2次治疗均于第14天达到骨髓完全缓解,且不良反应轻微。但CD19CAR-T细胞治疗缓解后2周骨髓复发,患者外周血检测到异常19CAR基因表达,同时TP53突变水平亦增高。最终CD22CAR-T细胞挽救治疗桥接单倍体造血干细胞移植后成功。由此表明在细胞制备过程中应进一步提高CD3+细胞纯度;CD22CAR-T治疗可以作为CD19CAR-T治疗复发的一个挽救治疗措施。

TCR-T免疫治疗肿瘤:现状、挑战及展望

T细胞受体工程T细胞(engineered T cell receptor-T cell,TCR-T)疗法和嵌合抗原受体T细胞(chimeric antigens receptor-T cell,CAR-T)疗法是目前过继性T细胞治疗最有效的两种方式。由于CAR仅能识别肿瘤表面的抗原,在实体瘤治疗中至今未有令人满意的结果。TCR不仅能识别肿瘤表面抗原,同时能识别胞内抗原,因此,TCR-T疗法在治疗实体瘤方面显示出前所未有的前景,成为极具潜力的治疗方式。本综述探讨了TCR-T疗法与CAR-T疗法识别癌症抗原机制的差异及当前TCR-T疗法靶向的临床靶点和不同类型的肿瘤抗原,描述了TCR-T抗肿瘤治疗的临床开发现状,并讨论了临床前评估TCR效价的标准和目前TCR-T治疗的优势、存在的局限性及可能有效的应对措施。最后,我们回顾了TCR-T治疗的现状和当前仍存在的一些挑战,强调靶向肿瘤特异性抗原的重要性,概述了结合检查点阻断治疗和溶瘤病毒等的新抗原特异性TCR-T治疗策略,以期这种联合治疗能够显著改善癌症的免疫治疗效果,并对未来TCR-T治疗根除多发性癌症提供一些思路。

Current status and perspectives of chimeric antigen receptor modified T cells for cancer treatment

Chimeric antigen receptor （CAR） is a recombinant immunoreceptor combining an antibody-derived target- ing fragment with signaling domains capable of acti- vating cells, which endows T cells with the ability to recognize tumor-associated surface antigens indepen- dent of the expression of major histocompatibiiity complex （MHC） molecules. Recent early-phase clinical trials of CAR-modified T （CAR-T） cells for relapsed or refractory B cell malignancies have demonstrated promising results （that is, anti-CD19 CAR-T in B cell acute lymphoblastic leukemia （B-ALL））. Given this suc- cess, broadening the clinical experience of CAR-T cell therapy beyond hematological malignancies has been actively investigated. Here we discuss the basic design of CAR and review the clinical results from the studies of CAR-T cells in B cell leukemia and lymphoma, and several solid tumors. We additionally discuss the major challenges in the further development and strategies for increasing anti-tumor activity and safety, as well as for successful commercial translation.

Blocking CD38-driven fratricide among T cells enables effective antitumor activity by CD38-specific chimeric antigen receptor T cells

Chimeric antigen receptor T-cell(CAR T) therapy is a kind of effective cancer immunotherapy. However,designing CARs remains a challenge because many targetable antigens are shared by T cells and tumor cells. This shared expression of antigens can cause CAR T cell fratricide. CD38-targeting approaches(e.g.,daratumumab) have been used in clinical therapy and have shown promising results. CD38 is a kind of surface glycoprotein present in a variety of cells, such as T lymphocytes and tumor cells. It was previously reported that CD38-based CAR T cells may undergo apoptosis or T cell-mediated killing(fratricide) during cell manufacturing. In this study, a CAR containing a sequence targeting human CD38 was designed to be functional. To avoid fratricide driven by CD38 and ensure the production of CAR T cells, two distinct strategies based on antibodies(clone MM12 T or clone MM27) or proteins(H02 H or H08 H) were used to block CD38 or the CAR single-chain variable fragment(scFv) domain, respectively, on the T cell surface.The results indicated that the antibodies or proteins, especially the antibody MM27, could affect CAR T cells by inhibiting fratricide while promoting expansion and enrichment. Anti-CD38 CAR T cells exhibited robust and specific cytotoxicity to CD38+ cell lines and tumor cells. Furthermore, the levels of the proinflammatory factors TNF-a, IFN-g and IL-2 were significantly upregulated in the supernatants of A549CD38+ cells. Finally, significant control of disease progression was demonstrated in xenograft mouse models. In conclusion, these findings will help to further enhance the expansion, persistence and function of anti-CD38 CAR T cells in subsequent clinical trials.

γδT cells:Major advances in basic and clinical research in tumor immunotherapy

γδT cells are a kind of innate immune T cell.They have not attracted sufficient attention because they account for only a small proportion of all immune cells,and many basic factors related to these cells remain unclear.However,in recent years,with the rapid development of tumor immunotherapy,γδT cells have attracted increasing attention because of their ability to exert cytotoxic effects on most tumor cells without major histocompatibility complex(MHC)restriction.An increasing number of basic studies have focused on the development,antigen recognition,activation,and antitumor immune response ofγδT cells.Additionally,γδT cell-based immunotherapeutic strategies are being developed,and the number of clinical trials investigating such strategies is increasing.This review mainly summarizes the progress of basic research and the clinical application ofγδT cells in tumor immunotherapy to provide a theoretical basis for further the development ofγδT cell-based strategies in the future.

过继性细胞免疫治疗在宫颈癌中的研究进展

宫颈癌是女性最常见的恶性肿瘤之一,复发或转移性宫颈癌5年生存率仅为17%,临床治疗十分棘手;程序性死亡受体1(programmed death-1,PD-1)单抗已用于复发或转移性宫颈癌一线治疗。但PD-1单抗单药治疗存在客观反应率低和易耐药等瓶颈,限制了临床应用。近年来,过继性细胞免疫治疗改变了癌症免疫治疗的格局。过继性细胞免疫治疗主要通过向体内回输具有抗肿瘤活性的免疫细胞,从而达到抗肿瘤的目的。目前过继性细胞免疫治疗主要有3种类型:肿瘤浸润性淋巴细胞、T细胞受体修饰T细胞和嵌合抗原受体T细胞。相关研究表明过继性细胞免疫治疗对改善晚期宫颈癌患者生存及预后具有重要价值。综述过继性细胞免疫治疗的原理、生物学特征、在宫颈癌治疗中的应用及局限性,以期通过优化其生产技术并与其他肿瘤治疗方式联合治疗,为提高宫颈癌免疫治疗疗效提供新的思路。

T细胞肿瘤免疫治疗的研究进展

随着科学技术的不断发展,人类对肿瘤疾病认识的不断深入,也带来了医学界对肿瘤治疗模式的改变。通过现代生物技术调节机体的免疫功能状态,利用人体自身免疫系统来治疗肿瘤疾病,并取得了很大的成效。肿瘤免疫治疗成为继手术、化疗和放疗之后的第四种有效治疗肿瘤的方法。用于肿瘤免疫治疗的细胞主要有:T淋巴细胞(T lymphocyte)、树突细胞(dendritic cell,DC)、自然杀伤细胞(natural killer cell,NK cell)、细胞因子诱导的杀伤细胞(cytokine-induced killer cell,CIK cell)以及DC-CIK细胞(dendritic cell-cytokine-induced killer cell)。在肿瘤的发生和发展过程中,T细胞介导的细胞免疫发挥着重要的作用。因此,探索T细胞肿瘤免疫治疗一直是肿瘤免疫研究领域的研究热点,现就T细胞相关的肿瘤免疫疗法研究进展作一综述。

CD87-targeted BiTE and CAR-T cells potently inhibit invasive nonfunctional pituitary adenomas

Recently,bispecific T-cell engagers(BiTEs)and chimeric antigen receptor-modified T cells(CAR-Ts)have been shown to have high therapeutic efficacy in hematological tumors.CD87 is highly expressed in solid tumors with an oncogenic function.To assess their cytotoxic effects on invasive nonfunctioning pituitary adenomas(iNFPAs),we first examined CD87 expression and its effects on the metabolism of iNFPA cells.We generated CD87-specific BiTE and CAR/IL-12 T cells,and their cytotoxic effects on iNFPAs cells and in mouse models were determined.CD87 had high expression in i NFPA tissue and cell samples but was undetected in noncancerous brain samples.CD87×CD3 BiTE and CD87 CAR/IL-12 T-cells showed antigenic specificity and exerted satisfactory cytotoxic effects,decreasing tumor cell proliferation in vitro and reducing existing tumors in experimental mice.Overall,the above findings suggest that CD87 is a promising target for the immunotherapeutic management of iNFPAs using anti-CD87 BiTE and CD87-specific CAR/IL-12 T cells.

靶向核抗原的嵌合抗原受体T细胞构建及其分泌IFN-γ功能验证

目的构建靶向实体瘤微环境嵌合抗原受体T细胞(CAR-T细胞),诱导微环境中IFN-γ的表达,以达到抗肿瘤的目的。方法筛选核抗原特异性单克隆抗体,通过基因工程技术构建嵌合抗原受体(CAR);将CAR亚克隆到慢病毒载体后转染HEK293细胞,包装成表达CAR的慢病毒,转导HEK293F细胞后,以流式细胞术检测CAR表达细胞比例判断转导效率;将CAR表达慢病毒转导活化T细胞后形成CAR-T细胞,采用流式细胞术检测在不同抗原(核小体抗原、Brefeldin A、二者联合)诱导下或核小体抗原单独诱导0、2、48 h时CAR-T细胞分泌IFN-γ情况。结果在培养10~15 d时,表达CAR的HEK293F细胞比例达53.04%~87.17%。在核小体抗原、Brefeldin A、二者联合组诱导下,分泌IFN-γ的T细胞比例分别为0.028%、0.034%、3.570%;核小体抗原诱导0、48 h时检测不到分泌IFN-γ的CAR-T细胞,2 h时分泌IFN-γ的CAR-T细胞最多。结论成功构建靶向核抗原的CAR-T细胞,且该细胞具有IFN-γ分泌功能。

嵌合抗原受体-T细胞免疫疗法在实体瘤中的进展及挑战

目前,嵌合抗原受体(CAR)-T细胞免疫疗法已在血液系统恶性肿瘤方面取得了显著成功,这给肿瘤免疫治疗带来革命性的改变,但CAR-T细胞在实体瘤的应用及其疗效并未达到预期的效果。与血液系统疾病相比,CAR-T细胞免疫疗法用于实体瘤时面临一系列独特的挑战。本综述回顾了CAR-T细胞的研究进展,指出CAR-T细胞在实体瘤治疗中的挑战和新策略,旨在为CAR-T细胞治疗实体瘤提供新的思路。

嵌合抗原受体T细胞免疫疗法治疗儿童恶性肿瘤的研究进展

嵌合抗原受体T细胞免疫疗法(CAR-T细胞疗法)是一种肿瘤免疫治疗方法,通过诱导T细胞的活化特异性识别肿瘤的靶点,释放细胞因子,发挥T细胞对肿瘤细胞的杀伤作用,可在共刺激因子协助下发挥持续的抗肿瘤作用。白血病、淋巴瘤等血液系统恶性肿瘤和神经母细胞瘤好发于儿童,具有较高的致死率,目前对于难治性和复发性肿瘤仍缺乏有效的治疗手段。随着CAR-T细胞疗法的研究深入,人们发现该法对上述儿童好发恶性肿瘤的治疗可发挥重要作用,对其难治性和复发性的病例也具有较好的疗效。本文将对CAR-T细胞疗法治疗儿童好发恶性肿瘤的相关研究进展进行综述。

CD19 CAR-T细胞治疗复发难治性急性B淋巴细胞白血病1例并文献复习

目的:观察以CD19为靶点的嵌合抗原受体T细胞(Chimeric Antigen Receptor T-Cell Immunotherapy,CAR-T)治疗复发难治性急性B淋巴细胞白血病的疗效并文献复习。方法:37岁女性,急性B淋巴细胞白血病多次化疗后复发,合并中枢神经系统白血病,化疗效果差。2016年5月28日在河南中医药大学第二附属医院回输CD19 CAR-T细胞每千克1.0×106个细胞。通过观察回输后的临床症状,评价是否存在细胞因子风暴及神经系统反应;通过检测骨髓象、免疫表型、微小残留病变等评估临床疗效;通过检测体内CD19+细胞比例和T细胞中CAR+细胞比例以及脱氧核糖核酸(DeoxyriboNucleic Acid,DNA)和血中嵌合抗原受体(Chimeric Antigen Receptor,CAR)的拷贝数,探讨CAR-T细胞在体内的作用过程以及患者长期缓解可能存在的原因。结果:CAR-T细胞回输后,白血病微小残留病变始终为阴性,脑脊液中始终未检测到白血病细胞;回输后初期CD19+细胞比例保持比较低的比例,但至第380天CD19+细胞有扩增趋势;DNA和血浆中CAR的拷贝数均在第9天达到高峰。回输后达完全缓解(CR)34个月。结论:CD19 CAR-T细胞是治疗复发难治性急性B淋巴细胞白血病的有效方法,同时对于中枢神经系统白血病的缓解有较好的疗效,但本病长期缓解的机制仍需进一步探讨。

过继性T细胞治疗在非小细胞肺癌中的研究进展

T细胞是获得性抗肿瘤免疫的重要细胞亚群,但肿瘤组织中的T细胞数量少,且处于免疫抑制甚至耗竭状态,这是导致肿瘤免疫逃逸和免疫检查点抑制剂等抗肿瘤免疫治疗效果不佳的重要原因。过继性T细胞治疗主要包括肿瘤浸润淋巴细胞(tumorinfiltrating lymphocytes,TILs)、嵌合抗原受体T细胞(chimeric antigen receptor T-cell,CAR-T)、T细胞受体工程化T细胞(T-cell receptor engineering T cell,TCR-T)治疗,其通过体外筛选扩增富集肿瘤特异性T细胞或通过基因改造赋予T细胞新的抗原特异性(CAR-T、TCR-T),有效克服了肿瘤浸润T细胞不足的缺陷。虽然过继性T细胞治疗在非小细胞肺癌(non-small cell lung cancer,NSCLC)中的研究起步较晚,但已显示治疗的安全可行性和初步抗肿瘤效果,值得进一步深入研究。本文将对TILs、CART、TCR-T的原理、培养方法、生物学特征以及在NSCLC治疗中的研究进展进行综述,以期为优化临床研究设计和开展新型NSCLC免疫治疗提供新思路。

肿瘤免疫细胞治疗的现状及展望

肿瘤免疫细胞治疗近年来因其疗效显著而备受瞩目。免疫细胞,包括T细胞、NK细胞和DC在抗肿瘤免疫应答以及肿瘤免疫治疗中发挥了重要作用。其中,嵌合抗原受体(chimeric antigen receptor,CAR)修饰T细胞(CAR-T)技术和逆转肿瘤免疫抑制功能的CTLA-4和PD-1/PD-L1等免疫检查点抑制剂疗法分别在血液肿瘤及黑素瘤等实体肿瘤治疗中取得了令人振奋的效果,如何进一步提高疗效、增加适应性肿瘤病种并控制其免疫相关的不良反应成为日后研究重点;NK细胞也将利用CAR技术和免疫检查点抑制剂进一步增强其在肿瘤治疗中的作用;DC作为第一个被FDA批准的治疗性肿瘤疫苗,在证明其安全无毒副作用的基础上,如何提高疗效成为关注热点。本文结合近年来肿瘤免疫细胞治疗的进展及该领域中亟需解决的问题作一分析与展望。