{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T09:39:12Z","timestamp":1768297152002,"version":"3.49.0"},"reference-count":127,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,4,16]],"date-time":"2020-04-16T00:00:00Z","timestamp":1586995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010621","name":"Uniwersytet Medyczny w Lublinie","doi-asserted-by":"publisher","award":["DS460"],"award-info":[{"award-number":["DS460"]}],"id":[{"id":"10.13039\/501100010621","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["UMO-2016\/21\/B\/NZ6\/02279"],"award-info":[{"award-number":["UMO-2016\/21\/B\/NZ6\/02279"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Despite the significant progress of modern anticancer therapies, multiple myeloma (MM) is still incurable for the majority of patients. Following almost three decades of development, chimeric antigen receptor (CAR) T-cell therapy now has the opportunity to revolutionize the treatment landscape and meet the unmet clinical need. However, there are still several major hurdles to overcome. Here we discuss the recent advances of CAR T-cell therapy for MM with an emphasis on future directions and possible risks. Currently, CAR T-cell therapy for MM is at the first stage of clinical studies, and most studies have focused on CAR T cells targeting B cell maturation antigen (BCMA), but other antigens such as cluster of differentiation 138 (CD138, syndecan-1) are also being evaluated. Although this therapy is associated with side effects, such as cytokine release syndrome and neurotoxicity, and relapses have been observed, the benefit\u2013risk balance and huge potential drive the ongoing clinical progress. To fulfill the promise of recent clinical trial success and maximize the potential of CAR T, future efforts should focus on the reduction of side effects, novel targeted antigens, combinatorial uses of different types of CAR T, and development of CAR T cells targeting more than one antigen.<\/jats:p>","DOI":"10.3390\/cells9040983","type":"journal-article","created":{"date-parts":[[2020,4,16]],"date-time":"2020-04-16T13:01:39Z","timestamp":1587042099000},"page":"983","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Paving the Way toward Successful Multiple Myeloma Treatment: Chimeric Antigen Receptor T-Cell Therapy"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0451-4741","authenticated-orcid":false,"given":"Ewelina","family":"Grywalska","sequence":"first","affiliation":[{"name":"Department of Clinical Immunology and Immunotherapy, Medical University of Lublin, 20-093 Lublin, Poland"},{"name":"St. John\u2019s Cancer Centre, 20-090 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Sosnowska-Pasiarska","sequence":"additional","affiliation":[{"name":"Department of Oncocardiology, Holy Cross Cancer Centre, 25-734 Kielce, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jolanta","family":"Smok-Kalwat","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, Holy Cross Cancer Centre, 25-734 Kielce, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcin","family":"Pasiarski","sequence":"additional","affiliation":[{"name":"Department of Immunology, Faculty of Health Sciences, Jan Kochanowski University, 25-317 Kielce, Poland"},{"name":"Department of Hematology, Holy Cross Cancer Centre, 25-734 Kielce, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4065-3842","authenticated-orcid":false,"given":"Paulina","family":"Nied\u017awiedzka-Rystwej","sequence":"additional","affiliation":[{"name":"Institute of Biology, University of Szczecin, 71-412 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5596-2651","authenticated-orcid":false,"given":"Jacek","family":"Roli\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology and Immunotherapy, Medical University of Lublin, 20-093 Lublin, Poland"},{"name":"St. John\u2019s Cancer Centre, 20-090 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4519","DOI":"10.1182\/blood-2011-06-358812","article-title":"Personalized therapy in multiple myeloma according to patient age and vulnerability: A report of the European Myeloma Network (EMN)","volume":"118","author":"Palumbo","year":"2011","journal-title":"Blood"},{"key":"ref_2","unstructured":"Atlanta: American Cancer Society (2019, December 15). Cancer Facts & Figures. Available online: https:\/\/www.cancer.org\/content\/dam\/cancer-org\/research\/cancer-facts-and-statistics\/annual-cancer-facts-and-figures\/2018\/cancer-facts-and-figures-2018.pdf."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s00277-018-3465-8","article-title":"Glucocorticoids in multiple myeloma: Past, present, and future","volume":"98","author":"Burwick","year":"2019","journal-title":"Ann. Hematol."},{"key":"ref_4","unstructured":"Neal, A.J., and Hoskin, P.J. (2012). Clinical Oncology, CRC Press. [4th ed.]."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"271","DOI":"10.2147\/tcrm.2006.2.3.271","article-title":"Bortezomib (Velcade\u2122) in the treatment of multiple myeloma","volume":"2","author":"Morgan","year":"2006","journal-title":"Ther. Clin. Risk Manag."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3968","DOI":"10.1182\/blood-2007-10-117457","article-title":"Thalidomide for treatment of multiple myeloma: 10 years later","volume":"111","author":"Palumbo","year":"2008","journal-title":"Blood"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1056\/NEJMoa1606038","article-title":"Daratumumab, bortezomib, and dexamethasone for multiple myeloma","volume":"375","author":"Palumbo","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1056\/NEJMra1011442","article-title":"Multiple myeloma","volume":"364","author":"Palumbo","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2516","DOI":"10.1182\/blood-2007-10-116129","article-title":"Improved survival in multiple myeloma and the impact of novel therapies","volume":"111","author":"Kumar","year":"2008","journal-title":"Blood"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1200\/JCO.2011.37.8919","article-title":"The 39th David A. Karnofsky Lecture: Bench-to-bedside translation of targeted therapies in multiple myeloma","volume":"30","author":"Anderson","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2208","DOI":"10.1038\/leu.2016.147","article-title":"Early relapse following initial therapy for multiple myeloma predicts poor outcomes in the era of novel agents","volume":"30","author":"Majithia","year":"2016","journal-title":"Leukemia"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.1038\/leu.2017.138","article-title":"Natural history of relapsed myeloma, refractory to immunomodulatory drugs and proteasome inhibitors: A multicenter IMWG study","volume":"31","author":"Kumar","year":"2017","journal-title":"Leukemia"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"iv52","DOI":"10.1093\/annonc\/mdx096","article-title":"Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"28","author":"Moreau","year":"2017","journal-title":"Ann. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.mayocp.2016.04.028","article-title":"The UK cancer drugs fund experiment and the US cancer drug cost problem: Bearing the cost of cancer drugs until it is unbearable","volume":"91","author":"Prasad","year":"2016","journal-title":"Mayo Clin. Proc."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1200\/EDBK_200867","article-title":"Value and Cost of Myeloma Therapy","volume":"38","author":"Rajkumar","year":"2018","journal-title":"Am. Soc. Clin. Oncol. Educ. Book"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Stock, S., Schmitt, M., and Sellner, L. (2019). Optimizing Manufacturing Protocols of Chimeric Antigen Receptor T Cells for Improved Anticancer Immunotherapy. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20246223"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1056\/NEJMra1706169","article-title":"Chimeric antigen receptor therapy","volume":"379","author":"June","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3010","DOI":"10.1200\/JCO.2017.72.8519","article-title":"Durable molecular remissions in chronic lymphocytic leukemia treated with CD19-specific chimeric antigen receptor-modified T cells after failure of ibrutinib","volume":"35","author":"Turtle","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2545","DOI":"10.1056\/NEJMoa1708566","article-title":"Chimeric antigen receptor T cells in refractory B-cell lymphomas","volume":"377","author":"Schuster","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.3389\/fimmu.2017.01956","article-title":"Differences in Expansion Potential of Naive Chimeric Antigen Receptor T Cells from Healthy Donors and Untreated Chronic Lymphocytic Leukemia Patients","volume":"8","author":"Hoffmann","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1056\/NEJMoa1709919","article-title":"Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia","volume":"378","author":"Park","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.omtm.2018.12.009","article-title":"Engineering and design of chimeric antigen receptors","volume":"12","author":"Guedan","year":"2019","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/nature22395","article-title":"Therapeutic T cell engineering","volume":"545","author":"Sadelain","year":"2017","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1073\/pnas.90.2.720","article-title":"Specific activation and targeting of cytotoxic lymphocytes through chimeric single chains consisting of antibody-binding domains and the \u03b3 or \u03b6 subunits of the immunoglobulin and T-cell receptors","volume":"90","author":"Eshhar","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1084\/jem.181.5.1653","article-title":"Signals through T cell receptor-zeta chain alone are insufficient to prime resting T lymphocytes","volume":"181","author":"Brocker","year":"1995","journal-title":"J. Exp. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/sj.neo.7900018","article-title":"Cancer patient T cells genetically targeted to prostate-specific membrane antigen specifically lyse prostate cancer cells and release cytokines in response to prostate-specific membrane antigen","volume":"1","author":"Gong","year":"1999","journal-title":"Neoplasia"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1084\/jem.188.4.619","article-title":"Antigen-dependent CD28 signaling selectively enhances survival and proliferation in genetically modified activated human primary T lymphocytes","volume":"188","author":"Krause","year":"1998","journal-title":"J. Exp. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1056\/NEJMoa1103849","article-title":"Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia","volume":"365","author":"Porter","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1182\/asheducation.V2012.1.143.3798224","article-title":"Novel cellular therapies for leukemia: CAR-modified T cells targeted to the CD19 antigen","volume":"2012","author":"Brentjens","year":"2012","journal-title":"Hematol. Am. Soc. Hematol. Educ. Program"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s40425-017-0230-9","article-title":"Current approaches to increase CAR T cell potency in solid tumors: Targeting the tumor microenvironment","volume":"5","author":"Maus","year":"2017","journal-title":"J. Immunother. Cancer"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1182\/blood-2003-06-2043","article-title":"Expression of BCMA, TACI, and BAFF-R in multiple myeloma: A mechanism for growth and survival","volume":"103","author":"Novak","year":"2004","journal-title":"Blood"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.ccell.2017.02.002","article-title":"Target expression, generation, preclinical activity, and pharmacokinetics of the BCMA-T cell bispecific antibody EM801 for multiple myeloma treatment","volume":"31","author":"Seckinger","year":"2017","journal-title":"Cancer Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3225","DOI":"10.1182\/blood-2016-01-691162","article-title":"APRIL and BCMA promote human multiple myeloma growth and immunosuppression in the bone marrow microenvironment","volume":"127","author":"Tai","year":"2016","journal-title":"Blood"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3148","DOI":"10.1182\/blood-2003-06-1984","article-title":"BAFF and APRIL protect myeloma cells from apoptosis induced by interleukin 6 deprivation and dexamethasone","volume":"103","author":"Moreaux","year":"2004","journal-title":"Blood"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"785","DOI":"10.3324\/haematol.2016.150896","article-title":"Serum B-cell maturation antigen: A novel biomarker to predict outcomes for multiple myeloma patients","volume":"102","author":"Ghermezi","year":"2017","journal-title":"Haematologica"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1111\/j.1365-2141.2012.09241.x","article-title":"Serum B-cell maturation antigen is elevated in multiple myeloma and correlates with disease status and survival","volume":"158","author":"Sanchez","year":"2012","journal-title":"Br. J. Haematol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1038\/35010115","article-title":"TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease","volume":"404","author":"Gross","year":"2000","journal-title":"Nature"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"9156","DOI":"10.1073\/pnas.160213497","article-title":"B cell maturation protein is a receptor for the tumor necrosis factor family member TALL-1","volume":"97","author":"Shu","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s11010-017-3136-4","article-title":"CD137-CD137L interaction modulates neointima formation and the phenotype transformation of vascular smooth muscle cells via NFATc1 signaling","volume":"439","author":"Zhong","year":"2018","journal-title":"Mol. Cell Biochem."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Gagelmann, N., Ayuk, F., Atanackovic, D., and Kr\u00f6ger, N. (2019). B cell maturation antigen-specific chimeric antigen receptor T cells for relapsed or refractory multiple myeloma: A meta-analysis. Eur. J. Haematol.","DOI":"10.1182\/blood-2019-121967"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1182\/blood-2016-04-711903","article-title":"T cells expressing an anti-B-cell maturation antigenchimeric antigen receptor cause remissions of multiple myeloma","volume":"128","author":"Ali","year":"2016","journal-title":"Blood"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1089\/hum.2018.001","article-title":"Effective targeting of multiple B-cell maturation antigen-expressing hematological malignances by anti-B-cell maturation antigen chimeric antigen receptor T cells","volume":"29","author":"Friedman","year":"2018","journal-title":"Hum. Gene Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.1056\/NEJMoa1817226","article-title":"Anti-BCMA CAR T-cell therapy bb2121 in relapsed or refractory multiple myeloma","volume":"380","author":"Raje","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1182\/blood-2018-99-116953","article-title":"Initial results from a phase 1 clinical study of bb21217, a next-generation anti Bcma CAR T therapy","volume":"132","author":"Shah","year":"2018","journal-title":"Blood"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1182\/blood-2018-99-110548","article-title":"Updated analysis of a phase 1, open-label study of LCAR-B38M, a chimeric antigen receptor T cell therapy directed against B-cell maturation antigen, in patients with relapsed\/refractory multiple myeloma","volume":"132","author":"Zhao","year":"2018","journal-title":"Blood"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1186\/s13045-018-0681-6","article-title":"A phase 1, open-label study of LCAR-B38M, a chimeric antigen receptor T cell therapy directed against B cell maturation antigen, in patients with relapsed or refractory multiple myeloma","volume":"11","author":"Zhao","year":"2018","journal-title":"J. Hematol. Oncol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"9543","DOI":"10.1073\/pnas.1819745116","article-title":"Exploratory trial of a biepitopic CAR T-targeting B cell maturation antigen in relapsed\/refractory multiple myeloma","volume":"116","author":"Xu","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","first-page":"120","article-title":"PiggyBac transposon vectors: The tools of the human gene encoding","volume":"5","author":"Zhao","year":"2016","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1182\/blood-2018-99-111419","article-title":"Efficacy and safety of P-Bcma-101 CAR-T cells in patients with relapsed\/refractory (r\/r) multiple myeloma (MM)","volume":"132","author":"Gregory","year":"2018","journal-title":"Blood"},{"key":"ref_50","first-page":"1813","article-title":"Development of JCARH125: Optimization of a fully human anti-Bcma CAR for use in the treatment of multiple myeloma","volume":"130","author":"Harrington","year":"2017","journal-title":"Blood"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1182\/blood-2018-99-113548","article-title":"JCARH125, anti-BCMA CAR T-cell therapy for relapsed\/refractory multiple myeloma: Initial proof of concept results from a phase 1\/2 multicenter study (EVOLVE)","volume":"132","author":"Mailankody","year":"2018","journal-title":"Blood"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1182\/blood-2018-99-113220","article-title":"Low dose of human scFv-derived BCMA-targeted CAR-T cells achieved fast response and high complete remission in patients with relapsed\/refractory multiple myeloma","volume":"132","author":"Jiang","year":"2018","journal-title":"Blood"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1182\/blood-2018-99-119717","article-title":"Clinical Responses and Pharmacokinetics of MCARH171, a Human-Derived Bcma Targeted CAR T Cell Therapy in Relapsed\/Refractory Multiple Myeloma: Final Results of a Phase I Clinical Trial","volume":"132","author":"Mailankody","year":"2018","journal-title":"Blood"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1186\/s13045-018-0672-7","article-title":"Anti-BCMA CAR-T cells for treatment of plasma cell dyscrasia: Case report on POEMS syndrome and multiple myeloma","volume":"11","author":"Xu","year":"2018","journal-title":"J. Hematol. Oncol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"8013","DOI":"10.1200\/JCO.2019.37.15_suppl.8013","article-title":"Clinical responses and pharmacokinetics of fully human BCMA targeting CAR T cell therapy in relapsed\/refractory multiple myeloma","volume":"37","author":"Li","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/2162-3619-1-36","article-title":"CD19: A biomarker for B cell development, lymphoma diagnosis and therapy","volume":"1","author":"Wang","year":"2012","journal-title":"Exp. Hematol. Oncol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.3324\/haematol.2015.138826","article-title":"The myeloma stem cell concept, revisited: From phenomenology to operational terms","volume":"101","author":"Johnsen","year":"2016","journal-title":"Haematologica"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1056\/NEJMoa1504542","article-title":"Chimeric antigen receptor T cells against CD19 for multiple myeloma","volume":"373","author":"Garfall","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"120505","DOI":"10.1172\/jci.insight.120505","article-title":"Anti-CD19 CAR T cells with high-dose melphalan and autologous stem cell transplantation for refractory multiple myeloma","volume":"3","author":"Garfall","year":"2018","journal-title":"JCI Insight"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s13045-016-0378-7","article-title":"Cocktail treatment with EGFR-specific and CD133-specific chimeric antigen receptor-modified T cells in a patient with advanced cholangiocarcinoma","volume":"10","author":"Feng","year":"2017","journal-title":"J. Hematol. Oncol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.1182\/blood-2018-99-111856","article-title":"Sequential CD19- and CD22-CART cell therapies for relapsed B-cell acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation","volume":"132","author":"Liu","year":"2018","journal-title":"Blood"},{"key":"ref_62","first-page":"506","article-title":"Combined infusion of CD19 and Bcma-specific chimeric antigen receptor T cells for RRMM: Initial safety and efficacy report from a clinical pilot study","volume":"130","author":"Yan","year":"2017","journal-title":"Blood"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1182\/blood-2018-99-117964","article-title":"Tandom autologous transplantation and combined infusion of CD19 and Bcma-specific chimeric antigen receptor T cells for high-risk MM: Initial safety and efficacy report from a clinical pilot study","volume":"132","author":"Shi","year":"2018","journal-title":"Blood"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1158\/2326-6066.CIR-15-0098","article-title":"NKG2D receptor and its ligands in host defense","volume":"3","author":"Lanier","year":"2015","journal-title":"Cancer Immunol. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"5944","DOI":"10.1038\/onc.2008.272","article-title":"NKG2D ligands in tumor immunity","volume":"27","author":"Nausch","year":"2008","journal-title":"Oncogene"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1158\/2326-6066.CIR-18-0307","article-title":"Phase I trial of autologous CAR T cells targeting NKG2D ligands in patients with AML\/MDS and multiple myeloma","volume":"7","author":"Baumeister","year":"2019","journal-title":"Cancer Immunol. Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.1172\/JCI128372","article-title":"BCMA CAR T cells: The winding path to success","volume":"130","author":"Borrello","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1182\/blood-2018-99-114522","article-title":"NKG2D-CAR transduced primary natural killer cells efficiently target multiple myeloma cells","volume":"132","author":"Leivas","year":"2018","journal-title":"Blood"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2588","DOI":"10.1172\/JCI86000","article-title":"Clinical responses with T lymphocytes targeting malignancy-associated kappa light chains","volume":"126","author":"Ramos","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2332","DOI":"10.1182\/blood-2003-09-3064","article-title":"Characterization of clonogenic multiple myeloma cells","volume":"103","author":"Matsui","year":"2004","journal-title":"Blood"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"328","DOI":"10.2119\/2006-00099.Lund","article-title":"Signaling properties of CD38 in the mouse immune system: Enzyme-dependent and -independent roles in immunity","volume":"12","author":"Lund","year":"2006","journal-title":"Mol. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1002\/cyto.b.21092","article-title":"CD38 and CD157: A long journey from activation markers to multifunctional molecules","volume":"84","author":"Quarona","year":"2013","journal-title":"Cytom. B Clin. Cytom."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1908","DOI":"10.1038\/leu.2012.120","article-title":"Euroflow antibody panels for standardized n-dimensional flow cytometric immunophenotyping of normal, reactive and malignant leukocytes","volume":"26","author":"Lhermitte","year":"2012","journal-title":"Leukemia"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1016\/S0140-6736(15)01120-4","article-title":"Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): An open-label, randomised, phase 2 trial","volume":"387","author":"Lonial","year":"2016","journal-title":"Lancet"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1038\/s41375-019-0536-3","article-title":"In vivo vaccination effect in multiple myeloma patients treated with the monoclonal antibody isatuximab","volume":"34","author":"Atanackovic","year":"2020","journal-title":"Leukemia"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.1016\/j.ymthe.2017.04.024","article-title":"A rational strategy for reducing on-target off-tumor effects of CD38-chimeric antigen receptors by affinity optimization","volume":"25","author":"Drent","year":"2017","journal-title":"Mol. Ther."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1038\/nm.3910","article-title":"NY-ESO-1-specific TCR-engineered T cells mediate sustained antigen-specific antitumor effects in myeloma","volume":"21","author":"Rapport","year":"2015","journal-title":"Nat. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1038\/gt.2012.48","article-title":"Effector memory and central memory NY-ESO-1-specific re-directed T cells for treatment of multiple myeloma","volume":"20","author":"Schuberth","year":"2013","journal-title":"Gene Ther."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1007\/s002510000274","article-title":"Molecular cloning of CS1, a novel human natural killer cell receptor belonging to the CD2 subset of the immunoglobulin superfamily","volume":"52","author":"Boles","year":"2001","journal-title":"Immunogenetics"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2775","DOI":"10.1158\/1078-0432.CCR-07-4246","article-title":"CS1, a potential new therapeutic antibody target for the treatment of multiple myeloma","volume":"14","author":"His","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e1308618","DOI":"10.1080\/2162402X.2017.1308618","article-title":"Novel anti-myeloma immunotherapies targeting the SLAM family of receptors","volume":"6","author":"Radhakrishnan","year":"2017","journal-title":"Oncoimmunology"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.clim.2018.10.006","article-title":"The role of surface molecule CD229 in Multiple Myeloma","volume":"204","author":"Olson","year":"2019","journal-title":"Clin. Immunol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"893","DOI":"10.2147\/DDDT.S98053","article-title":"Clinical potential of SLAMF7 antibodies\u2014Focus on elotuzumab in multiple myeloma","volume":"11","author":"Friend","year":"2017","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2838","DOI":"10.1182\/blood-2017-04-778423","article-title":"SLAMF7-CAR T cells eliminate myeloma and confer selective fratricide of SLAMF7+ normal lymphocytes","volume":"130","author":"Gogishvili","year":"2017","journal-title":"Blood"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1038\/s41416-018-0325-1","article-title":"Teaching an old dog new tricks: Next-generation CAR T cells","volume":"120","author":"Tokarew","year":"2019","journal-title":"Br. J. Cancer"},{"key":"ref_86","first-page":"502","article-title":"Universal SLAMF7-specific CAR T-cells as treatment for multiple myeloma","volume":"130","author":"Mathur","year":"2017","journal-title":"Blood"},{"key":"ref_87","first-page":"489","article-title":"CD44v6, a target for novel antibody treatment approaches, is frequently expressed in multiple myeloma and associated with deletion of chromosome arm 13q","volume":"90","author":"Liebisch","year":"2005","journal-title":"Haematologica"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"6064","DOI":"10.1158\/1078-0432.CCR-06-0910","article-title":"A phase I dose-escalation study with anti-CD44v6 bivatuzumab mertansine in patients with incurable squamous cell carcinoma of the head and neck or esophagus","volume":"12","author":"Tijink","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"3461","DOI":"10.1182\/blood-2013-04-493361","article-title":"CD44v6-targeted T cells mediate potent antitumor effects against acute myeloid leukemia and multiple myeloma","volume":"122","author":"Casucci","year":"2013","journal-title":"Blood"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1182\/blood.V76.2.377.377","article-title":"Plasma cells in multiple myeloma express a natural killer cell-associated antigen: CD56 (NKH-1; Leu-19)","volume":"76","author":"Durie","year":"1990","journal-title":"Blood"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"4629","DOI":"10.1158\/0008-5472.CAN-04-0142","article-title":"In vitro and in vivo activity of the maytansinoid immunoconjugate huN901-N2\u2032-deacetyl-N2\u2032-(3-mercapto-1-oxopropyl)-maytansine against CD56+ multiple myeloma cells","volume":"64","author":"Tassone","year":"2004","journal-title":"Cancer Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"163","DOI":"10.2741\/4202","article-title":"Lorvotuzumab mertansine: Antibody-drug-conjugate for CD56+ multiple myeloma","volume":"19","author":"Berdeja","year":"2014","journal-title":"Front. Biosci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"3499","DOI":"10.1158\/1538-7445.AM2012-3499","article-title":"CD56 targeted chimeric antigen receptors for immunotherapy of multiple myeloma","volume":"72","author":"Benjamin","year":"2012","journal-title":"Cancer Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"7763","DOI":"10.1158\/1078-0432.CCR-08-0493","article-title":"Preclinical characterization of SGN-70, a humanized antibody directed against CD70","volume":"14","author":"McEarchern","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1097\/01.pai.0000159773.50905.7b","article-title":"Utility of syndecan-1 (CD138) expression in the diagnosis of undifferentiated malignant neoplasms: A tissue microarray study of 1,754 cases","volume":"13","author":"Kambham","year":"2005","journal-title":"Appl. Immunohistochem. Mol. Morphol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/s00280-015-2909-2","article-title":"First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70","volume":"77","author":"Owonikoko","year":"2016","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2267","DOI":"10.1158\/1078-0432.CCR-16-1421","article-title":"Preclinical evaluation of chimeric antigen receptors targeting CD70-expressing cancers","volume":"23","author":"Wang","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1093\/neuonc\/nox116","article-title":"CD70, a novel target of CAR T-cell therapy for gliomas","volume":"20","author":"Jin","year":"2018","journal-title":"Neuro Oncol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"13100","DOI":"10.1016\/S0021-9258(17)36804-7","article-title":"Fine structure of heparan sulfate regulates syndecan-1 function and cell behavior","volume":"269","author":"Sanderson","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1089\/jir.2014.0125","article-title":"Anti-CD138-targeted interferon is a potent therapeutic against multiple myeloma","volume":"35","author":"Yoo","year":"2015","journal-title":"J. Interferon Cytokine Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1182\/blood.V118.21.305.305","article-title":"BT062, An antibody-drug conjugate directed against CD138, shows clinical activity in patients with relapsed or relapsed\/refractory multiple myeloma","volume":"118","author":"Jagannath","year":"2011","journal-title":"Blood"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"4486","DOI":"10.1182\/blood.V128.22.4486.4486","article-title":"Indatuximab ravtansine (BT062) in combination with low-dose dexamethasone and lenalidomide or pomalidomide: Clinical activity in patients with relapsed\/refractory multiple myeloma","volume":"128","author":"Kelly","year":"2016","journal-title":"Blood"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.3389\/fimmu.2019.01613","article-title":"Chimeric Antigen Receptor-Modified T Cell Therapy in Multiple Myeloma: Beyond B Cell Maturation Antigen","volume":"10","author":"Timmers","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.jocit.2014.11.001","article-title":"CD138-directed adoptive immunotherapy of chimeric antigen receptor (CAR)-modified T cells for multiple myeloma","volume":"2","author":"Guo","year":"2016","journal-title":"J. Cell Immunother."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.18632\/oncotarget.26792","article-title":"Safety and efficacy of targeting CD138 with a chimeric antigen receptor for the treatment of multiple myeloma","volume":"10","author":"Sun","year":"2019","journal-title":"Oncotarget"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1111\/j.1365-2362.2012.02679.x","article-title":"Overexpression of G protein-coupled receptor 5D in the bone marrow is associated with poor prognosis in patients with multiple myeloma","volume":"42","author":"Atamaniuk","year":"2012","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1179\/1607845413Y.0000000079","article-title":"GPRC5D is a promising marker for monitoring the tumor load and to target multiple myeloma cells","volume":"18","author":"Cohen","year":"2013","journal-title":"Hematology"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"eaau7746","DOI":"10.1126\/scitranslmed.aau7746","article-title":"GPRC5D is a target for the immunotherapy of multiple myeloma with rationally designed CAR T cells","volume":"11","author":"Smith","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1182\/blood-2018-99-110471","article-title":"CAR T cell therapy targeting G protein-coupled receptor class c group 5 member D (GPRC5D), a novel target for the immunotherapy of multiple myeloma","volume":"132","author":"Smith","year":"2018","journal-title":"Blood"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1182\/blood-2017-05-781351","article-title":"An APRIL-based chimeric antigen receptor for dual targeting of BCMA and TACI in multiple myeloma","volume":"131","author":"Lee","year":"2018","journal-title":"Blood"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1158\/1078-0432.CCR-13-0168","article-title":"Zoom zoom: Racing CARs for multiple myeloma","volume":"19","author":"Maus","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1038\/nm.4431","article-title":"The activated conformation of integrin \u03b27 is a novel multiple myeloma-specific target for CAR T cell therapy","volume":"23","author":"Hosen","year":"2017","journal-title":"Nat. Med."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1038\/s41375-018-0242-6","article-title":"APRIL signaling via TACI mediates immunosuppression by T regulatory cells in multiple myeloma: Therapeutic implications","volume":"33","author":"Tai","year":"2019","journal-title":"Leukemia"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.3324\/haematol.2010.036814","article-title":"Surface molecule CD229 as a novel target for the diagnosis and treatment of multiple myeloma","volume":"96","author":"Atanackovic","year":"2011","journal-title":"Haematologica"},{"key":"ref_115","first-page":"3142","article-title":"Chimeric antigen receptor (CAR) T cells specific for CD229: A potentially curative approach for multiple myeloma","volume":"130","author":"Luetkens","year":"2017","journal-title":"Blood"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1182\/blood-2008-06-161281","article-title":"Regulation of multiple myeloma survival and progression by CD1d","volume":"113","author":"Spanoudakis","year":"2009","journal-title":"Blood"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1182\/blood-2014-05-552729","article-title":"Current concepts in the diagnosis and management of cytokine release syndrome","volume":"124","author":"Lee","year":"2014","journal-title":"Blood"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"224ra25","DOI":"10.1126\/scitranslmed.3008226","article-title":"Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia","volume":"6","author":"Davila","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1056\/NEJMoa1215134","article-title":"Chimeric antigen receptor-modified T cells for acute lymphoid leukemia","volume":"368","author":"Grupp","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.bbmt.2018.09.024","article-title":"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","volume":"25","author":"Mahmoudjafari","year":"2019","journal-title":"Biol. Blood Marrow Transpl."},{"key":"ref_121","first-page":"1","article-title":"Anti-BCMA chimeric antigen receptors with fully human heavy-chain-only antigen recognition domains","volume":"11","author":"Lam","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.retram.2018.03.003","article-title":"Insights into cytokine release syndrome and neurotoxicity after CD19-specific CAR-T cell therapy","volume":"66","author":"Gauthier","year":"2018","journal-title":"Curr. Res. Transl. Med."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s13045-018-0571-y","article-title":"Grading of cytokine release syndrome associated with the CAR T cell therapy tisagenlecleucel","volume":"11","author":"Porter","year":"2018","journal-title":"J. Hematol. Oncol."},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Drent, E., Poels, R., Mulders, M.J., van de Donk, N.W.C.J., Themeli, M., Lokhorst, H.M., and Mutis, T. (2018). Feasibility of controlling CD38-CAR T cell activity with a Tet-on inducible CAR design. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0197349"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/s41586-019-1054-1","article-title":"CAR T cell trogocytosis and cooperative killing regulate tumor antigen escape","volume":"568","author":"Hamieh","year":"2019","journal-title":"Nature"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/leu.2017.302","article-title":"A compound chimeric antigen receptor strategy for targeting multiple myeloma","volume":"32","author":"Chen","year":"2018","journal-title":"Leukemia"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"146","DOI":"10.3389\/fonc.2019.00146","article-title":"Multi-targeted CART cell therapies for B-cell malignancies","volume":"9","author":"Shah","year":"2019","journal-title":"Front. Oncol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/4\/983\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:09:11Z","timestamp":1760364551000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/4\/983"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,16]]},"references-count":127,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,4]]}},"alternative-id":["cells9040983"],"URL":"https:\/\/doi.org\/10.3390\/cells9040983","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,16]]}}}