Journal of Zhejiang University-SCIENCE B

, Volume 21, Issue 1, pp 29–41 | Cite as

Current advances in chimeric antigen receptor T-cell therapy for refractory/relapsed multiple myeloma

  • He HuangEmail author
  • Heng-wei Wu
  • Yong-xian Hu


multiple myeloma (MM), considered an incurable hematological malignancy, is characterized by its clonal evolution of malignant plasma cells. Although the application of autologous stem cell transplantation (ASCT) and the introduction of novel agents such as immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs) have doubled the median overall survival to eight years, relapsed and refractory diseases are still frequent events in the course of MM. To achieve a durable and deep remission, immunotherapy modalities have been developed for relapsed/refractory multiple myeloma (RRMM). Among these approaches, chimeric antigen receptor (CAR) T-cell therapy is the most promising star, based on the results of previous success in B-cell neoplasms. In this immunotherapy, autologous T cells are engineered to express an artificial receptor which targets a tumor-associated antigen and initiates the T-cell killing procedure. Tisagenlecleucel and Axicabtagene, targeting the CD19 antigen, are the two pacesetters of CAR T-cell products. They were approved by the US Food and Drug Administration (FDA) in 2017 for the treatment of acute lymphocytic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL). Their development enabled unparalleled efficacy in combating hematopoietic neoplasms. In this review article, we summarize six promising candidate antigens in MM that can be targeted by CARs and discuss some noteworthy studies of the safety profile of current CAR T-cell therapy.

Key words

Chimeric antigen receptor (CAR) T cells Immunotherapy Monoclonal antibody (mAb) Target antigen Multiple myeloma 

嵌合抗原受体 T 细胞在治疗难治/复发多发性骨髓瘤中的新进展


多发性骨髓瘤被认为是一种无法治愈的血液系统恶性疾病, 其特征为恶性浆细胞的克隆性增殖. 尽管在过去的几十年中, 自体干细胞移植 (ASCT) 的应用及新型药物 (蛋白酶体抑制剂和免疫调节药) 的问世, 将患者的中位生存时间由原来的 4 年提高到了 8 年, 但复发与难治仍然是多发性骨髓瘤疾病进程中难以逾越的鸿沟. 为了获得长期持续的缓解, 免疫治疗开始在多发性骨髓瘤中崭露头角, 其中嵌合抗原受体 (CAR) T 细胞治疗就是最有潜力的一颗新星. 通过在基因层面改造患者自己的 T 细胞, 使 T 细胞表达一种特定的受体 (人造的融合蛋白), 该受体可以识别并结合肿瘤相关抗原, 并活化 T 细胞启动后续的杀伤过程. Tisagenlecleucel 和 Axicabtagene 是两个针对 CD19 抗原的 CAR T 产品, 用于治疗 B 细胞来源的急性淋巴细胞白血病 (B-ALL) 和弥漫大 B 细胞淋巴瘤 (DLBCL), 并于 2017 年被美国食品药品监督管理局 (FDA)批准. 这两个产品的发展极大推动了 B 细胞来源的恶性血液系统疾病的治疗, 并刷新了对于传统治疗的认知. 基于之前 CAR T 治疗的成功经验, 寻找如 CD19 一样的特定靶点能为 CAR T 治疗多发性骨髓瘤打下基础. 本综述介绍了数个在骨髓瘤细胞上的肿瘤靶抗原, 如 B 细胞成熟抗原 (BCMA) 和 CD38. 这些针对抗原的 CAR T 治疗有些还在实验室阶段, 而有些已经进入了 3 期的临床试验, 很有可能成为下一个被批准的 CAR T 产品. 另外, 本综述也介绍了在 CAR T 治疗中出现的毒副反应以及相应的管理和处理方法.


嵌合抗原受体 (CAR) T 细胞 免疫治疗 单克隆抗体 靶抗原 多发性骨髓瘤 

CLC number



Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.



He HUANG took the lead in writing the manuscript. Heng-wei WU wrote and edited the manuscript. Yong-xian HU contributed to shaping the tables and figures. All authors read and approved the final manuscript and, therefore, had full access to all the data in the study and take responsibility for the integrity and security of the data.

Compliance with ethics guidelines

He HUANG, Heng-wei WU, and Yong-xian HU declare that they have no conflict of interest.

This article does not contain any studies with human or animal subjects performed by any of the authors.


  1. Ali SA, Shi V, Maric I, et al., 2016. T cells expressing an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of multiple myeloma. Blood, 128(13): 1688–1700. PubMedPubMedCentralGoogle Scholar
  2. American Cancer Society, 2019. Cancer Facts & Figures 2019. American Cancer Society, Atlanta, GA, USA.Google Scholar
  3. Anderson KC, 2012. The 39th David A. Karnofsky Lecture: bench-to-bedside translation of targeted therapies in multiple myeloma. J Clin Oncol, 30(4):445–452. PubMedPubMedCentralGoogle Scholar
  4. Atamaniuk J, Gleiss A, Porpaczy E, et al., 2012. Overexpression of G protein-coupled receptor 5D in the bone marrow is associated with poor prognosis in patients with multiple myeloma. Eur J Clin Invest, 42(9):953–960. PubMedGoogle Scholar
  5. Becker N, 2011. Epidemiology of multiple myeloma. In: Moehler T, Goldschmidt H (Eds.), Multiple Myeloma. Recent Results in Cancer Research, Vol. 183. Springer, Berlin, Heidelberg, p.25–35. Google Scholar
  6. Boles KS, Mathew PA, 2001. Molecular cloning of CS1, a novel human natural killer cell receptor belonging to the CD2 subset of the immunoglobulin superfamily. Immunogenetics, 52(3–4):302–307. PubMedGoogle Scholar
  7. Brentjens R, Yeh R, Bernal Y, et al., 2010. Treatment of chronic lymphocytic leukemia with genetically targeted autologous T cells: case report of an unforeseen adverse event in a phase I clinical trial. Mol Ther, 18(4):666–668. PubMedPubMedCentralGoogle Scholar
  8. Brudno JN, Kochenderfer JN, 2016. Toxicities of chimeric antigen receptor T cells: recognition and management. Blood, 127(26):3321–3330. PubMedPubMedCentralGoogle Scholar
  9. Calpe S, Wang NH, Romero X, et al., 2008. The SLAM and SAP gene families control innate and adaptive immune responses. Adv Immunol, 97:177–250. PubMedGoogle Scholar
  10. Carpenter RO, Evbuomwan MO, Pittaluga S, et al., 2013. B-cell maturation antigen is a promising target for adoptive T-cell therapy of multiple myeloma. Clin Cancer Res, 19(8):2048–2060. PubMedPubMedCentralGoogle Scholar
  11. Chekmasova AA, Horton HM, Garrett TE, et al., 2015. A novel and highly potent CAR T cell drug product for treatment of BCMA-expressing hematological malignances. Blood, 126(23):3094. Google Scholar
  12. Chen J, Zhong MC, Guo HJ, et al., 2017. SLAMF7 is critical for phagocytosis of haematopoietic tumour cells via Mac-1 integrin. Nature, 544(7651):493–497. PubMedPubMedCentralGoogle Scholar
  13. Chillemi A, Quarona V, Antonioli L, et al., 2017. Roles and modalities of ectonucleotidases in remodeling the multiple myeloma niche. Front Immunol, 8:305. PubMedPubMedCentralGoogle Scholar
  14. Cohen Y, Gutwein O, Garach-Jehoshua O, et al., 2013. GPRC5D is a promising marker for monitoring the tumor load and to target multiple myeloma cells. Hematology, 18(6):348–351. PubMedGoogle Scholar
  15. Cremer FW, Bila J, Buck I, et al., 2005. Delineation of distinct subgroups of multiple myeloma and a model for clonal evolution based on interphase cytogenetics. Genes Chromosomes Cancer, 44(2):194–203. PubMedGoogle Scholar
  16. Davila ML, Riviere I, Wang XY, et al., 2014. Efficacy and toxicity management of 19–28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci Transl Med, 6(224): 224ra25. PubMedPubMedCentralGoogle Scholar
  17. Deaglio S, Mehta K, Malavasi F, 2001. Human CD38: a (r)evolutionary story of enzymes and receptors. Leuk Res, 25(1):1–12. PubMedGoogle Scholar
  18. Dianzani U, Funaro A, DiFranco D, et al., 1994. Interaction between endothelium and CD4+CD45RA+ lymphocytes: role of the human CD38 molecule. J Immunol, 153(3): 952–959.PubMedGoogle Scholar
  19. Drent E, Groen RWJ, Noort WA, et al., 2016. Pre-clinical evaluation of CD38 chimeric antigen receptor engineered T cells for the treatment of multiple myeloma. Haematologica, 101(5):616–625. PubMedPubMedCentralGoogle Scholar
  20. Drent E, Themeli M, Poels R, et al., 2017. A rational strategy for reducing on-target off-tumor effects of CD38-chimeric antigen receptors by affinity optimization. Mol Ther, 25(8): 1946–1958. PubMedPubMedCentralGoogle Scholar
  21. Drent E, Poels R, Mulders MJ, et al., 2018. Feasibility of controlling CD38-CAR T cell activity with a Tet-on inducible CAR design. PLoS ONE, 13(5):e0197349. PubMedPubMedCentralGoogle Scholar
  22. Eshhar Z, Waks T, Gross G, et al., 1993. Specific activation and targeting of cytotoxic lymphocytes through chimeric single chains consisting of antibody-binding domains and the γ or ζ subunits of the immunoglobulin and T-cell receptors. Proc Natl Acad Sci USA, 90(2):720–724. PubMedGoogle Scholar
  23. Friend R, Bhutani M, Voorhees PM, et al., 2017. Clinical potential of SLAMF7 antibodies—focus on elotuzumab in multiple myeloma. Drug Des Devel Ther, 11:893–900. PubMedPubMedCentralGoogle Scholar
  24. Frigyesi I, Adolfsson J, Ali M, et al., 2014. Robust isolation of malignant plasma cells in multiple myeloma. Blood, 123(9):1336–1340. PubMedGoogle Scholar
  25. Funaro A, Spagnoli GC, Ausiello CM, et al., 1990. Involvement of the multilineage CD38 molecule in a unique pathway of cell activation and proliferation. J Immunol, 145(8):2390–2396.PubMedGoogle Scholar
  26. Gao Y, Wang XL, Yan HL, et al., 2016. Comparative transcriptome analysis of fetal skin reveals key genes related to hair follicle morphogenesis in cashmere goats. PLoS ONE, 11(3):e0151118. PubMedPubMedCentralGoogle Scholar
  27. Gauthier J, Turtle CJ, 2018. Insights into cytokine release syndrome and neurotoxicity after CD19-specific CAR-T cell therapy. Curr Res Transl Med, 66(2):50–52. PubMedPubMedCentralGoogle Scholar
  28. Gogishvili T, Danhof S, Prommersberger S, et al., 2017. SLAMF7-CAR T cells eliminate myeloma and confer selective fratricide of SLAMF7+ normal lymphocytes. Blood, 130(26):2838–2847. PubMedGoogle Scholar
  29. Grupp SA, Kalos M, Barrett D, et al., 2013. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med, 368(16):1509–1518. PubMedPubMedCentralGoogle Scholar
  30. Guedan S, Calderon H, Posey AD Jr, et al., 2019. Engineering and design of chimeric antigen receptors. Mol Ther Methods Clin Dev, 12:145–156. PubMedGoogle Scholar
  31. Guo B, Chen MX, Han QW, et al., 2016. CD138-directed adoptive immunotherapy of chimeric antigen receptor (CAR)-modified T cells for multiple myeloma. J Cell Immunother, 2(1):28–35. Google Scholar
  32. He Y, Bouwstra R, Wiersma VR, et al., 2019. Cancer cell-expressed SLAMF7 is not required for CD47-mediated phagocytosis. Nat Commun, 10(1):533. PubMedPubMedCentralGoogle Scholar
  33. Hideshima T, Mitsiades C, Tonon G, et al., 2007. Understanding multiple myeloma pathogenesis in the bone marrow to identify new therapeutic targets. Nat Rev Cancer, 7(8): 585–598. PubMedGoogle Scholar
  34. Hipp S, Tai YT, Blanset D, et al., 2017. Erratum: a novel BCMA/CD3 bispecific T-cell engager for the treatment of multiple myeloma induces selective lysis in vitro and in vivo. Leukemia, 31(10):2278. PubMedGoogle Scholar
  35. Howard M, Grimaldi JC, Bazan JF, et al., 1993. Formation and hydrolysis of cyclic ADP-ribose catalyzed by lymphocyte antigen CD38. Science, 262(5136):1056–1059. PubMedGoogle Scholar
  36. Hsi ED, Steinle R, Balasa B, et al., 2008. CS1, a potential new therapeutic antibody target for the treatment of multiple myeloma. Clin Cancer Res, 14(9):2775–2784. PubMedPubMedCentralGoogle Scholar
  37. Ibrahim S, Keating M, Do KA, et al., 2001. CD38 expression as an important prognostic factor in B-cell chronic lymphocytic leukemia. Blood, 98(1):181–186. PubMedGoogle Scholar
  38. Inoue S, Nambu T, Shimomura T, 2004. The RAIG family member, GPRC5D, is associated with hard-keratinized structures. J Invest Dermatol, 122(3):565–573. PubMedGoogle Scholar
  39. Kim YJ, Yoon B, Han K, et al., 2017. Comprehensive transcriptome profiling of balding and non-balding scalps in trichorhinophalangeal syndrome type I patient. Ann Dermatol, 29(5):597–601. PubMedPubMedCentralGoogle Scholar
  40. Kochenderfer JN, Dudley ME, Kassim SH, et al., 2015. Chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies can be effectively treated with autologous T cells expressing an anti-CD19 chimeric antigen receptor. J Clin Oncol, 33(6):540–549. PubMedGoogle Scholar
  41. Krejcik J, Casneuf T, Nijhof IS, et al., 2016. Daratumumab depletes CD38+ immune regulatory cells, promotes T-cell expansion, and skews T-cell repertoire in multiple myeloma. Blood, 128(3):384–394. PubMedPubMedCentralGoogle Scholar
  42. Kumar SK, Rajkumar SV, Dispenzieri A, et al., 2008. Improved survival in multiple myeloma and the impact of novel therapies. Blood, 111(5):2516–2520. PubMedPubMedCentralGoogle Scholar
  43. Kumar SK, Dimopoulos MA, Kastritis E, et al., 2017. Natural history of relapsed myeloma, refractory to immunomodulatory drugs and proteasome inhibitors: a multicenter IMWG study. Leukemia, 31(11):2443–2448. PubMedGoogle Scholar
  44. Kyle RA, Rajkumar SV, 2004. Multiple myeloma. N Engl J Med, 351(18):1860–1873. PubMedGoogle Scholar
  45. Lam L, Chin L, Halder RC, et al., 2016. Epigenetic changes in T-cell and monocyte signatures and production of neurotoxic cytokines in ALS patients. FASEB J, 30(10):3461–3473. PubMedPubMedCentralGoogle Scholar
  46. Le RQ, Li L, Yuan WS, et al., 2018. FDA approval summary: tocilizumab for treatment of chimeric antigen receptor T cell-induced severe or life-threatening cytokine release syndrome. Oncologist, 23(8):943–947. PubMedPubMedCentralGoogle Scholar
  47. Lee DW, Gardner R, Porter DL, et al., 2014. Current concepts in the diagnosis and management of cytokine release syndrome. Blood, 124(2):188–195. PubMedPubMedCentralGoogle Scholar
  48. Lokhorst HM, Plesner T, Laubach JP, et al., 2015. Targeting CD38 with daratumumab monotherapy in multiple myeloma. N Engl J Med, 373(13):1207–1219. PubMedGoogle Scholar
  49. Lonial S, Weiss BM, Usmani SZ, et al., 2016. Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomised, phase 2 trial. Lancet, 387(10027):1551–1560. PubMedGoogle Scholar
  50. Ludwig H, Durie BGM, Bolejack V, et al., 2008. Myeloma in patients younger than age 50 years presents with more favorable features and shows better survival: an analysis of 10549 patients from the international myeloma working group. Blood, 111(8):4039–4047. PubMedPubMedCentralGoogle Scholar
  51. Lund FE, 2006. Signaling properties of CD38 in the mouse immune system: enzyme-dependent and -independent roles in immunity. Mol Med, 12(11–12):328–333. PubMedPubMedCentralGoogle Scholar
  52. Mahmoudjafari Z, Hawks KG, Hsieh AA, et al., 2019. American Society for Blood and Marrow Transplantation Pharmacy Special Interest Group survey on chimeric antigen receptor T cell therapy administrative, logistic, and toxicity management practices in the United States. Biol Blood Marrow Transpl, 25(1):26–33. Google Scholar
  53. Maude SL, Teachey DT, Porter DL, et al., 2015. CD19-targeted chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia. Blood, 125(26):4017–4023. PubMedPubMedCentralGoogle Scholar
  54. Maude SL, Laetsch TW, Buechner J, et al., 2018. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med, 378(5):439–448. PubMedPubMedCentralGoogle Scholar
  55. Mihara K, Bhattacharyya J, Kitanaka A, et al., 2012. T-cell immunotherapy with a chimeric receptor against CD38 is effective in eliminating myeloma cells. Leukemia, 26(2): 365–367. PubMedGoogle Scholar
  56. Moreau P, San Miguel J, Sonneveld P, et al., 2017. Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol, 28(Suppl 4): iv52–iv61. PubMedGoogle Scholar
  57. Neelapu SS, Tummala S, Kebriaei P, et al., 2018. Chimeric antigen receptor T-cell therapy—assessment and management of toxicities. Nat Rev Clin Oncol, 15(1):47–62. PubMedGoogle Scholar
  58. Novak AJ, Darce JR, Arendt BK, et al., 2004. Expression of BCMA, TACI, and BAFF-R in multiple myeloma: a mechanism for growth and survival. Blood, 103(2):689–694. PubMedGoogle Scholar
  59. O’Connell FP, Pinkus JL, Pinkus GS, 2004. CD138 (syndecan-1), a plasma cell marker: immunohistochemical profile in hematopoietic and nonhematopoietic neoplasms. Am J Clin Pathol, 121(2):254–263. PubMedGoogle Scholar
  60. O’Connor BP, Raman VS, Erickson LD, et al., 2004. BCMA is essential for the survival of long-lived bone marrow plasma cells. J Exp Med, 199(1):91–98. PubMedPubMedCentralGoogle Scholar
  61. Palaiologou M, Delladetsima I, Tiniakos D, 2014. CD138 (syndecan-1) expression in health and disease. Histol Histopathol, 29(2):177–189. PubMedGoogle Scholar
  62. Palumbo A, Chanan-Khan A, Weisel K, et al., 2016. Daratumumab, bortezomib, and dexamethasone for multiple myeloma. N Engl J Med, 375(8):754–766. PubMedGoogle Scholar
  63. Paus R, Nickoloff BJ, Ito T, 2005. A ‘hairy’ privilege. Trends Immunol, 26(1):32–40. PubMedGoogle Scholar
  64. Philip B, Kokalaki E, Mekkaoui L, et al., 2014. A highly compact epitope-based marker/suicide gene for easier and safer T-cell therapy. Blood, 124(8):1277–1287. PubMedGoogle Scholar
  65. Porter D, Frey N, Wood PA, et al., 2018. Grading of cytokine release syndrome associated with the CAR T cell therapy tisagenlecleucel. J Hematol Oncol, 11:35. PubMedPubMedCentralGoogle Scholar
  66. Quarona V, Zaccarello G, Chillemi A, et al., 2013. CD38 and CD157: a long journey from activation markers to multifunctional molecules. Cytometry B Clin Cytom, 84B(4): 207–217. Google Scholar
  67. Raje N, Berdeja J, Lin Y, et al., 2019. Anti-BCMA CAR T-cell therapy bb2121 in relapsed or refractory multiple myeloma. N Engl J Med, 380(18):1726–1737. PubMedGoogle Scholar
  68. Rajkumar SV, Blood E, Vesole D, et al., 2006. Phase III clinical trial of thalidomide plus dexamethasone compared with dexamethasone alone in newly diagnosed multiple myeloma: a clinical trial coordinated by the Eastern Co-operative Oncology Group. J Clin Oncol, 24(3):431–436. PubMedGoogle Scholar
  69. Ramos CA, Savoldo B, Torrano V, et al., 2016. Clinical responses with T lymphocytes targeting malignancy-associated κ light chains. J Clin Invest, 126(7):2588–2596. PubMedPubMedCentralGoogle Scholar
  70. Ren SS, Deng JW, Hong M, et al., 2019. Ethical considerations of cellular immunotherapy for cancer. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 20(1):23–31. Google Scholar
  71. Richardson P, Mitsiades C, Schlossman R, et al., 2007. The treatment of relapsed and refractory multiple myeloma. Hematology Am Soc Hematol Educ Program, 2007(1): 317–323. Google Scholar
  72. Rickert RC, Jellusova J, Miletic AV, 2011. Signaling by the tumor necrosis factor receptor superfamily in B-cell biology and disease. Immunol Rev, 244(1):115–133. PubMedPubMedCentralGoogle Scholar
  73. Sadelain M, Brentjens R, Rivière I, 2013. The basic principles of chimeric antigen receptor design. Cancer Discov, 3(4): 388–398. PubMedPubMedCentralGoogle Scholar
  74. Sanchez E, Li MJ, Kitto A, et al., 2012. Serum B-cell maturation antigen is elevated in multiple myeloma and correlates with disease status and survival. Br J Haematol, 158(6):727–738. PubMedGoogle Scholar
  75. Schwartzberg PL, Mueller KL, Qi H, et al., 2009. SLAM receptors and SAP influence lymphocyte interactions, development and function. Nat Rev Immunol, 9(1):39–46. PubMedGoogle Scholar
  76. Seckinger A, Delgado JA, Moser S, et al., 2017. Target expression, generation, preclinical activity, and pharmacokinetics of the BCMA-T cell bispecific antibody EM801 for multiple myeloma treatment. Cancer Cell, 31(3):396–410. PubMedGoogle Scholar
  77. Singhal S, Mehta J, Desikan R, et al., 1999. Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med, 341(21):1565–1571. PubMedGoogle Scholar
  78. Smith EL, Harrington K, Staehr M, et al., 2019. GPRC5D is a target for the immunotherapy of multiple myeloma with rationally designed CAR T cells. Sci Transl Med, 11(485): eaau7746. PubMedGoogle Scholar
  79. Stewart AK, Chang H, Trudel S, et al., 2007. Diagnostic evaluation of t(4;14) in multiple myeloma and evidence for clonal evolution. Leukemia, 21(11):2358–2359. PubMedGoogle Scholar
  80. Straathof KC, Pulè MA, Yotnda P, et al., 2005. An inducible caspase 9 safety switch for T-cell therapy. Blood, 105(11): 4247–4254. PubMedPubMedCentralGoogle Scholar
  81. Sun C, Mahendravada A, Ballard B, et al., 2019. Safety and efficacy of targeting CD138 with a chimeric antigen receptor for the treatment of multiple myeloma. Oncotarget, 10(24):2369–2383. PubMedPubMedCentralGoogle Scholar
  82. Tai YT, Dillon M, Song WH, et al., 2008. Anti-CS1 humanized monoclonal antibody Huluc63 inhibits myeloma cell adhesion and induces antibody-dependent cellular cytotoxicity in the bone marrow milieu. Blood, 112(4):1329–1337. PubMedPubMedCentralGoogle Scholar
  83. Terstappen LWMM, Huang SA, Safford M, et al., 1991. Sequential generations of hematopoietic colonies derived from single nonlineage-committed CD34+CD38 progenitor cells. Blood, 77(6):1218–1227.PubMedGoogle Scholar
  84. Touzeau C, Moreau P, Dumontet C, 2017. Monoclonal antibody therapy in multiple myeloma. Leukemia, 31(5):1039–1047. PubMedGoogle Scholar
  85. van Dongen JJM, Lhermitte L, Böttcher S, et al., 2012. Euroflow antibody panels for standardized n-dimensional flow cytometric immunophenotyping of normal, reactive and malignant leukocytes. Leukemia, 26(9):1908–1975. PubMedPubMedCentralGoogle Scholar
  86. Wang XJ, Marr AK, Breitkopf T, et al., 2014. Hair follicle mesenchyme-associated PD-L1 regulates T-cell activation induced apoptosis: a potential mechanism of immune privilege. J Invest Dermatol, 134(3):736–745. PubMedGoogle Scholar
  87. Westgate GE, Craggs RI, Gibson WT, 1991. Immune privilege in hair growth. J Invest Dermatol, 97(3):417–420. PubMedGoogle Scholar
  88. Wu N, Veillette A, 2016. SLAM family receptors in normal immunity and immune pathologies. Curr Opin Immunol, 38:45–51. PubMedGoogle Scholar
  89. Yoo EM, Trinh KR, Tran D, et al., 2015. Anti-CD 138-targeted interferon is a potent therapeutic against multiple myeloma. J Interferon Cytokine Res, 35(4):281–291. PubMedPubMedCentralGoogle Scholar

Copyright information

© Zhejiang University and Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Bone Marrow Transplantation Center, the First Affiliated Hospital, School of MedicineZhejiang UniversityHangzhouChina
  2. 2.Institute of HematologyZhejiang UniversityHangzhouChina

Personalised recommendations