嵌合抗原受体修饰T细胞研究进展及肿瘤靶抗原的选择

唐海军 刘玉琴

解剖学报 ›› 2017, Vol. 48 ›› Issue (1) : 115-120.

PDF(245 KB)
欢迎访问《解剖学报》官方网站!今天是 English
PDF(245 KB)
解剖学报 ›› 2017, Vol. 48 ›› Issue (1) : 115-120. DOI: 10.16098/j.issn.0529-1356.2017.01.021
综述

嵌合抗原受体修饰T细胞研究进展及肿瘤靶抗原的选择

  • 唐海军 刘玉琴*
作者信息 +

Development of chimeric antigen receptor modified T cells and the selection of tumor target antigen

  • TANG Hai-jun LIU Yu-qin*
Author information +
文章历史 +

摘要

嵌合抗原受体修饰T细胞(CAR-T)是目前恶性肿瘤免疫治疗的一种新方法。CAR-T细胞对肿瘤的杀伤不依赖主要组织相容性复合体(MHC),并可克服肿瘤局部免疫抑制微环境和突破宿主免疫耐受状态,因此,CAR-T细胞在治疗肿瘤方面具有独特的优势。CAR-T细胞的构建和选择合适的靶分子是CAR-T细胞免疫治疗的两个关键的问题,我们在文中将围绕这两个问题做一综述。

Abstract

Chimeric antigen receptor modified T cells (CAR-T) has been an emerging immunotherapy modality for malignant tumor. The cytotoxicity efficiency of CAR-T cells to tumor is independent of the major histocompatibility complex (MHC). CAR-T cells can overcome the immunity suppression in the microenvironmet of the tumor site and break out the immunological tolerance of the host. Thus it has its own advantages in the immunotherapy for tumors. The construction of CAR-T cells and the selection of appropriate tumor target molecules are the two key challengs in CAR-T cell immunotherapy, this review will focus on these two issues.

关键词

嵌合抗原受体 / 肿瘤 / 免疫治疗

Key words

Chimeric antigen receptor / Tumor / Immunotherapy

引用本文

导出引用
唐海军 刘玉琴. 嵌合抗原受体修饰T细胞研究进展及肿瘤靶抗原的选择[J]. 解剖学报. 2017, 48(1): 115-120 https://doi.org/10.16098/j.issn.0529-1356.2017.01.021
TANG Hai-jun LIU Yu-qin. Development of chimeric antigen receptor modified T cells and the selection of tumor target antigen[J]. Acta Anatomica Sinica. 2017, 48(1): 115-120 https://doi.org/10.16098/j.issn.0529-1356.2017.01.021

参考文献

[1]Gross G, Waks T, Eshhar Z. Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity[J]. Proc Natl Acad Sci USA, 1989,86(24):10024-10028.
[2]Mazzarella L. Tales from the Jazz ASH: highlights from the 2013 American Society of Haematology meeting[J]. E Cancer Medical Science, 2014,8:390.
[3]Grupp SA, Kalos M, Barrett D, et al. Chimeric antigen receptor modified T cells for acute lymphoid leukemia[J]. N Engl J Med, 2013,368(16):1509-1518.
[4]Kenderian SS, Ruella M, Gill S, et al. Chimeric antigen receptor T-cell therapy to target hematologic malignancies[J]. Cancer Res, 2014,74(22):6383-6389.
[5]Stephan MT, Ponomarev V, Brentjens RJ,et al. T cell-encoded CD80 and 4-1BBL induce auto- and transcostimulation, resulting in potent tumor rejection[J]. Nat Med,2007, 13(12):1440-1449.
[6]Eshhar Z,Waks T,Gross G,et al. Specific activation and targeting of cytotoxic lymphocytes through chimeric single chains consisting of antibody-binding domains and the gamma or zeta subunits of the immunoglobulin and T-cell receptors[J]. Proc Natl Acad Sci USA, 1993,90(2):720-724.
[7]Brocker T,Karjalainen K. Signals through T cell receptor-zeta chain alone are insufficient to prime resting T lymphocytes[J]. J Exp Med, 1995,181(5):1653-1659.
[8]Porter DL, Levine BL, Kalos M, et al. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia[J]. N Engl J Med, 2011,365(8):725-733.
[9]Burns WR, Zhao Y, Frankel TL, et al. A high molecular weight melanoma-associated antigen-specific chimeric antigen receptor redirects lymphocytes to target human melanomas[J]. Cancer Res, 2010,70(8):3027-3033.
[10]Zhao Y, Wang QJ,Yang S, et al. A herceptin-based chimeric antigen receptor with modified signaling domains leads to enhanced survival of transduced T lymphocytes and antitumor activity[J]. J Immunol, 2009,183(9):5563-5574.
[11]Carpenito C, Milone MC, Hassan R, et al. Control of large, established tumor xenografts with genetically retargeted human T cells containing CD28 and CD137 domains[J]. Proc Natl Acad Sci USA, 2009,106(9):3360-3365.
[12]Morgan RA, Yang JC, Kitano M, et al. Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2[J]. Mol Ther, 2010,18(4):843-851.
[13]Robbins PF,Morgan RA, Feldman SA, et al. Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1[J]. J Clin Oncol, 2011, 29(7):917-924.
[14]Kalos M, Levine BL, Porter DL, et al. T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia[J]. Sci Transl Med, 2011,3(95):95ra73.
[15]Brentjens RJ, Riviere I, Park JH, et al. Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias[J]. Blood, 2011,118(18):4817-4828.
[16]Kochenderfer JN, Dudley ME, Feldman SA, et al. B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor-transduced T cells[J]. Blood, 2012,119(12):2709-2720.
[17]Kloss CC, Condomines M, Cartellieri M, et al. Combinatorial antigen recognition with balanced signaling promotes selective tumor eradication by engineered T cells[J]. Nat Biotechnol, 2013,31(1):71-75.
[18]Rosenberg SA. Finding suitable targets is the major obstacle to cancer gene therapy[J]. Cancer Gene Ther, 2014,21(2):45-47.
[19]Arteaga CL, Sliwkowski MX, Osborne CK, et al. Treatment of HER2-positive breast cancer: current status and future perspectives[J]. Nat Rev Clin Oncol, 2012,9(1):16-32.
[20]Xu XJ,Tang YM. Cytokine release syndrome in cancer immunotherapy with chimeric antigen receptor engineered T cells[J]. Cancer Lett, 2014,343(2):172-178.
[21]Cooper LJ, Topp MS, Serrano LM, et al. T-cell clones can be rendered specific for CD19: toward the selective augmentation of the graft-versus-B-lineage leukemia effect[J]. Blood, 2003,101(4):1637-1644.
[22]Kochenderfer JN, Wilson WH, Janik JE, et al. Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19[J]. Blood, 2010,116(20):4099-4102.
[23]Kochenderfer JN, Rosenberg SA. Treating B-cell cancer with T cells expressing anti-CD19 chimeric antigen receptors[J]. Nat Rev Clin Oncol, 2013,10(5):267-276.
[24]Wang CT, Zhang P, Wang YS, et al. RNA- interference against Biot2, a novel mouse testis-specific gene, inhibits the growth of tumor cells[J]. Cell Mol Biol Lett, 2009,14(3):363-376.
[25]Chen YT, Scanlan MJ, Sahin U, et al. A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening[J]. Proc Natl Acad Sci USA, 1997,94(5):1914-1918.
[26]Gan HK, Cvrljevic AN, Johns TG. The epidermal growth factor receptor variant III (EGFRvIII): where wild things are altered[J]. FEBS J, 2013,280(21):5350-5370.
[27]Choi BD, Suryadevara CM, Gedeon PC, et al. Intracerebral delivery of a third generation EGFRvIII-specific chimeric antigen receptor is efficacious against human glioma[J]. J Clin Neurosci, 2014,21(1):189-190.
[28]Miao H, Choi BD, Suryadevara CM, et al. EGFRvIII-specific chimeric antigen receptor T cells migrate to and kill tumor deposits infiltrating the brain parenchyma in an invasive xenograft model of glioblastoma[J]. PLoS One, 2014,9(4):e94281.
[29]Tang X, Zhou Y, Li W, et al. T cells expressing a LMP1-specific chimeric antigen receptor mediate antitumor effects against LMP1-positive nasopharyngeal carcinoma cells in vitro and in vivo[J]. J Biomed Res, 2014,28(6):468-475.
[30]Chinnasamy D, Yu Z, Theoret MR, et al. Gene therapy using genetically modified lymphocytes targeting VEGFR-2 inhibits the growth of vascularized syngenic tumors in mice[J]. J Clin Invest, 2010,120(11):3953-3968.
[31]Tran E, Chinnasamy D, Yu Z, et al. Immune targeting of fibroblast activation protein triggers recognition of multipotent bone marrow stromal cells and cachexia[J]. J Exp Med, 2013,210(6):1125-1135.
[32]Robbins PF, Lu YC, El-Gamil M, et al. Mining exomic sequencing data to identify mutated antigens recognized by adoptively transferred tumor-reactive T cells[J]. Nat Med, 2013,19(6):747-752.
[33]Lu YC, Yao X, Crystal JS, et al. Efficient identification of mutated cancer antigens recognized by T cells associated with durable tumor regressions[J]. Clin Cancer Res, 2014,20(13):3401-3410.
[34]Geng W, Zhang ChY, Zhang FQ, et al. Role of cord blood-derived T lymphocytes transplanting for BALB/c mice with erythroleukemia[J]. Acta Anatomica Sinica, 2009, 40(1):57-62. (in Chinese)
耿微,张春燕,张福琴,等. 脐血源性 T淋巴细胞移植在 BALB/c 小鼠红白血病治疗中的作用[J].解剖学报,2009,40(1):57-62.
[35]Maude SL, Frey N, Shaw PA, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia[J]. N Engl J Med, 2014,371(16):1507-1517.
[36]Porter DL,Hwang WT,Frey NV,et al. Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia[J]. Sci Transl Med, 2015,7(303):303.
[37]Ahmed N, Brawley VS, Hegde M,et al. Human epidermal growth factor receptor 2 (HER2)-specific chimeric antigen receptor-modified T cells for the immunotherapy of HER2-positive sarcoma[J].J Clin Oncol, 2015,33(15):1688-1696.
[38]Beatty GL, Haas AR, Maus MV, et al. Mesothelin-specific chimeric antigen receptor mRNA-engineered T cells induce anti-tumor activity in solid malignancies[J]. Cancer Immunol Res, 2014, 2(2): 112-120.
[39]Maus MV, Haas AR, Beatty GL, et al. T cells expressing chimeric antigen receptors can cause anaphylaxis in humans[J]. Cancer Immunol Res, 2013, 1(1): 26-31.
[40]Katz SC, Burga RA, McCormack E, et al. Phase I hepatic immunotherapy for metastases study of intra-arterial chimeric antigen receptor-modified T-cell therapy for CEA+liver metastases[J]. Clin Cancer Res, 2015, 21(14):3149-3159.
[41]Lamers CH, Sleijfer S, van Steenbergen S, et al. Treatment of metastatic renal cell carcinoma with CAIX CAR-engineered T cells: clinical evaluation and management of on-target toxicity[J]. Mol Ther, 2013,21(4):904-912.
[42]Gargett T, Brown MP. The inducible caspase-9 suicide gene system as a “safety switch” to limit on-target, off-tumor toxicities of chimeric antigen receptor T cells[J]. Front Pharmacol, 2014,5:235.
[43]Davila ML, Kloss CC, Gunset G, et al. CD19 CAR-targeted T cells induce long-term remission and B cell aplasia in an immunocompetent mouse model of B cell acute lymphoblastic leukemia[J]. PLoS One, 2013,8(4):e61338.
[44]Grupp SA, Kalos M, Barrett D, et al. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia[J]. N Engl J Med, 2013,368(16):1509-1518.

基金

国家科技基础条件平台


PDF(245 KB)

Accesses

Citation

Detail

段落导航
相关文章

/