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Immunological reviews
09, 2021;303 (1): 154-167.

On the road to eliminating long-lived plasma cells-"are we there yet?"

Caroline Markmann, Vijay G Bhoj
Author Information
  1. Caroline Markmann: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.
  2. Vijay G Bhoj: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA. ORCID
PMID: 34351644 DOI: 10.1111/imr.13015

Abstract

Central to protective humoral immunity is the activation of B cells and their terminal differentiation into antibody-secreting plasma cells. Long-lived plasma cells (LLPC) may survive for years to decades. Such long-lived plasma cells are also responsible for producing pathogenic antibodies that cause a variety of challenges such as autoimmunity, allograft rejection, and drug neutralization. Up to now, various therapeutic strategies aimed at durably eliminating pathogenic antibodies have failed, in large part due to their inability to efficiently target LLPCs. Several antibody-based therapies have recently gained regulatory approval or are in clinical phases of development for the treatment of multiple myeloma, a malignancy of plasma cells. We discuss the exciting potential of using these emerging cancer immunotherapies to solve the antibody problem.

Keywords

immunotherapy long-lived PCs pathogenic antibodies

References

  1. Mullard A. FDA approves first BCMA-targeted CAR-T cell therapy. Nat Rev Drug Discov. 2021;20:332.
  2. Chatham WW, Kimberly RP. Treatment of lupus with corticosteroids. Lupus. 2001;10:140-147.
  3. Coutinho AE, Chapman KE. The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights. Mol Cell Endocrinol. 2011;335:2-13.
  4. Settipane G, Pudupakkam R, Mcgowan J. Corticosteroid effect on immunoglobulins. J Allergy Clin Immunol. 1978;62(3):162-166.
  5. McMillan R, Longmire R, Yelenosky R. The effect of corticosteroids on human IgG synthesis. J Immunol. 1976;116:1592-1595.
  6. Butler WT, Rossen RD. Effects of corticosteroids on immunity in man. I. Decreased serum IgG concentration caused by 3 or 5 days of high doses of methylprednisolone. J Clin Invest. 1973;52:2629-2640.
  7. Tiburzy B, Kulkarni U, Hauser AE, Abram M, Manz RA. Plasma cells in immunopathology: concepts and therapeutic strategies. Semin Immunopathol. 2014;36:277-288.
  8. Miller JJ, Cole LJ. Resistance of long-lived lymphocytes and plasma cells in rat lymph nodes to treatment with prednisone, cyclophosphamide, 6-mercaptopurine, and actinomycin D. J Exp Med. 1967;126:109-125.
  9. Hoes JN, Jacobs JWG, Verstappen SMM, Bijlsma JWJ, Van der Heijden GJMG. Adverse events of low- to medium-dose oral glucocorticoids in inflammatory diseases: a meta-analysis. Ann Rheum Dis. 2009;68(12):1833-1838.
  10. George MD, Baker JF, Winthrop K, et al. Risk for Serious Infection With Low-Dose Glucocorticoids in Patients With Rheumatoid Arthritis : A Cohort Study. Ann Intern Med. 2020;173:870-878.
  11. Padmanabhan A, Connelly-Smith L, Aqui N, et al. Guidelines on the Use of Therapeutic Apheresis in Clinical Practice - Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Eighth Special Issue. J Clin Apher. 2019;34:171-354.
  12. Schwab I, Nimmerjahn F. Intravenous immunoglobulin therapy: how does IgG modulate the immune system? Nat Rev Immunol. 2013;13:176-189.
  13. Jordan SC, Lorant T, Choi J, et al. IgG Endopeptidase in Highly Sensitized Patients Undergoing Transplantation. N Engl J Med. 2017;377:442-453.
  14. Lorant T, Bengtsson M, Eich T, et al. Safety, immunogenicity, pharmacokinetics, and efficacy of degradation of anti-HLA antibodies by IdeS (imlifidase) in chronic kidney disease patients. Am J Transplant. 2018;18:2752-2762.
  15. Lonze BE, Tatapudi VS, Weldon EP, et al. IdeS (Imlifidase): A Novel Agent That Cleaves Human IgG and Permits Successful Kidney Transplantation Across High-strength Donor-specific Antibody. Ann Surg. 2018;268:488-496.
  16. Leborgne C, Barbon E, Alexander JM, et al. IgG-cleaving endopeptidase enables in vivo gene therapy in the presence of anti-AAV neutralizing antibodies. Nat Med. 2020;26:1096-1101.
  17. Froissart A, Buffet M, Veyradier A, et al. Efficacy and safety of first-line rituximab in severe, acquired thrombotic thrombocytopenic purpura with a suboptimal response to plasma exchange. Experience of the French Thrombotic Microangiopathies Reference Center. Crit Care Med. 2012;40:104-111.
  18. Lim W, Vesely SK, George JN. The role of rituximab in the management of patients with acquired thrombotic thrombocytopenic purpura. Blood. 2015;125:1526-1531.
  19. Albert D, Dunham J, Khan S, et al. Variability in the biological response to anti-CD20 B cell depletion in systemic lupus erythaematosus. Ann Rheum Dis. 2008;67:1724-1731.
  20. Bailly E, Ville S, Blancho G, et al. An extension of the RITUX-ERAH study, multicenter randomized clinical trial comparing rituximab to placebo in acute antibody-mediated rejection after renal transplantation. Transpl Int. 2020;33:786-795.
  21. Redfield RR, Jordan SC, Busque S, et al. Safety, pharmacokinetics, and pharmacodynamic activity of obinutuzumab, a type 2 anti-CD20 monoclonal antibody for the desensitization of candidates for renal transplant. Am J Transplant. 2019;19:3035-3045.
  22. Macklin PS, Morris PJ, Knight SR. A systematic review of the use of rituximab for the treatment of antibody-mediated renal transplant rejection. Trans Rev. 2017;31(2):87-95.
  23. Hammers CM, Chen J, Lin C, et al. Persistence of anti-desmoglein 3 IgG(+) B-cell clones in pemphigus patients over years. J Invest Dermatol. 2015;135:742-749.
  24. Reff ME, Carner K, Chambers KS, et al. Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood. 1994;83:435-445.
  25. Audia S, Samson M, Guy J, et al. Immunologic effects of rituximab on the human spleen in immune thrombocytopenia. Blood. 2011;118:4394-4400.
  26. Genberg H, Hansson A, Wernerson A, Wennberg L, Tyden G. Pharmacodynamics of rituximab in kidney allotransplantation. Am J Transplant. 2006;6:2418-2428.
  27. Kozlowski T, Andreoni K. Limitations of rituximab/IVIg desensitization protocol in kidney transplantation; is this better than a tincture of time? Ann Transplant. 2011;16:19-25.
  28. Marfo K, Ling M, Bao Y, et al. Lack of effect in desensitization with intravenous immunoglobulin and rituximab in highly sensitized patients. Transplantation. 2012;94:345-351.
  29. Valenzuela NM, Reed EF. Antibody-mediated rejection across solid organ transplants: manifestations, mechanisms, and therapies. J Clin Invest. 2017;127:2492-2504.
  30. Bingham CO, Looney RJ, Deodhar A, et al. Immunization responses in rheumatoid arthritis patients treated with rituximab: results from a controlled clinical trial. Arthritis Rheum. 2010;62:64-74.
  31. Kamburova EG, Koenen HJPM, Borgman KJE, ten Berge IJ, Joosten I, Hilbrands LB. A single dose of rituximab does not deplete B cells in secondary lymphoid organs but alters phenotype and function. Am J Transplant. 2013;13:1503-1511.
  32. Nakou M, Katsikas G, Sidiropoulos P, et al. Rituximab therapy reduces activated B cells in both the peripheral blood and bone marrow of patients with rheumatoid arthritis: depletion of memory B cells correlates with clinical response. Arthritis Res Ther. 2009;11:R131.
  33. Thaunat O, Patey N, Gautreau C, et al. B cell survival in intragraft tertiary lymphoid organs after rituximab therapy. Transplantation. 2008;85:1648-1653.
  34. Wallin EF, Jolly EC, Suchánek O, et al. Human T-follicular helper and T-follicular regulatory cell maintenance is independent of germinal centers. Blood. 2014;124:2666-2674.
  35. Citrin R, Foster JB, Teachey DT. The role of proteasome inhibition in the treatment of malignant and non-malignant hematologic disorders. Expert Rev Hematol. 2016;9:873-889.
  36. Carlin Walsh R, Alloway RR, Girnita AL, Steve Woodle E. Proteasome inhibitor-based therapy for antibody-mediated rejection. Kidney Int. 2012;81:1067-1074.
  37. Philogene MC, Sikorski P, Montgomery RA, Leffell MS, Zachary AA. Differential effect of bortezomib on HLA class I and class II antibody. Transplantation. 2014;98:660-665.
  38. Peperzak V, Vikström I, Walker J, et al. Mcl-1 is essential for the survival of plasma cells. Nat Immunol. 2013;14:290-297.
  39. Kwun J, Matignon M, Manook M, et al. Daratumumab in Sensitized Kidney Transplantation: Potentials and Limitations of Experimental and Clinical Use. J Am Soc Nephrol. 2019;30:1206-1219.
  40. Schuster SJ, Bishop MR, Tam CS, et al. Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma. N Engl J Med. 2019;380:45-56.
  41. Raje N, Berdeja J, Lin Y, et al. Anti-BCMA CAR T-Cell Therapy bb2121 in Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2019;380:1726-1737.
  42. Cohen AD, Garfall AL, Stadtmauer EA, et al. B cell maturation antigen-specific CAR T cells are clinically active in multiple myeloma. J Clin Invest. 2019;129:2210-2221.
  43. Gross G, Waks T, Eshhar Z. Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity. Proc Natl Acad Sci U S A. 1989;86:10024-10028.
  44. Pinthus JH, et al. Immuno-gene therapy of established prostate tumors using chimeric receptor-redirected human lymphocytes. Cancer Res. 2003;63:2470-2476.
  45. Brocker T, Karjalainen K. Adoptive tumor immunity mediated by lymphocytes bearing modified antigen-specific receptors. Adv Immunol. 1998;68:257-269.
  46. Brentjens RJ, Latouche JB, Santos E, et al. Eradication of systemic B-cell tumors by genetically targeted human T lymphocytes co-stimulated by CD80 and interleukin-15. Nat Med. 2003;9:279-286.
  47. O'Leary MC, Lu X, Huang Y, et al. FDA Approval Summary: Tisagenlecleucel for Treatment of Patients with Relapsed or Refractory B-cell Precursor Acute Lymphoblastic Leukemia. Clin Cancer Res. 2019;25:1142-1146.
  48. Beyar-Katz O, Gill S. Advances in chimeric antigen receptor T cells. Curr Opin Hematol. 2020;27:368-377.
  49. Abramson JS, Palomba ML, Gordon LI, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet. 2020;396:839-852.
  50. Munshi NC, Anderson LD, Shah N, et al. Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma. N Engl J Med. 2021;384:705-716.
  51. Halliley JL, Tipton CM, Liesveld J, et al. Long-Lived Plasma Cells Are Contained within the CD19(-)CD38(hi)CD138(+) Subset in Human Bone Marrow. Immunity. 2015;43:132-145.
  52. Mei HE, Wirries I, Frölich D, et al. A unique population of IgG-expressing plasma cells lacking CD19 is enriched in human bone marrow. Blood. 2015;125:1739-1748.
  53. Bhoj VG, Arhontoulis D, Wertheim G, et al. Persistence of long-lived plasma cells and humoral immunity in individuals responding to CD19-directed CAR T-cell therapy. Blood. 2016;128:360-370.
  54. Milone MC, Bhoj VG. The Pharmacology of T Cell Therapies. Mol Ther Methods Clin Dev. 2018;8:210-221.
  55. Hill JA, Krantz EM, Hay KA, et al. Durable preservation of antiviral antibodies after CD19-directed chimeric antigen receptor T-cell immunotherapy. Blood Adv. 2019;3:3590-3601.
  56. Zhang Z, Schuster SJ, Lacey SF, Milone MC, Monos D, Bhoj VG. Stable HLA antibodies following sustained CD19+ cell depletion implicate a long-lived plasma cell source. Blood Adv. 2020;4:4292-4295.
  57. Kushner CJ, Wang S, Tovanabutra N, Tsai DE, Werth VP, Payne AS. Factors Associated With Complete Remission After Rituximab Therapy for Pemphigus. JAMA Dermatol. 2019;155:1404-1409.
  58. Joly P, Maho-Vaillant M, Prost-Squarcioni C, et al. First-line rituximab combined with short-term prednisone versus prednisone alone for the treatment of pemphigus (Ritux 3): a prospective, multicentre, parallel-group, open-label randomised trial. Lancet. 2017;389:2031-2040.
  59. Kim TH, Choi Y, Lee SE, Lim JM, Kim SC. Adjuvant rituximab treatment for pemphigus: A retrospective study of 45 patients at a single center with long-term follow up. J Dermatol. 2017;44:615-620.
  60. Westwood JP, Webster H, McGuckin S, McDonald V, Machin SJ, Scully M. Rituximab for thrombotic thrombocytopenic purpura: benefit of early administration during acute episodes and use of prophylaxis to prevent relapse. J Thromb Haemost. 2013;11:481-490.
  61. Sun L, Mack J, Li A, et al. Predictors of relapse and efficacy of rituximab in immune thrombotic thrombocytopenic purpura. Blood Adv. 2019;3:1512-1518.
  62. Parvathaneni K, Scott DW. Engineered FVIII-expressing cytotoxic T cells target and kill FVIII-specific B cells in vitro and in vivo. Blood Adv. 2018;2:2332-2340.
  63. Ellebrecht CT, Bhoj VG, Nace A, et al. Reengineering chimeric antigen receptor T cells for targeted therapy of autoimmune disease. Science. 2016;353:179-184.
  64. Perry DK, Pollinger HS, Burns JM, et al. Two novel assays of alloantibody-secreting cells demonstrating resistance to desensitization with IVIG and rATG. Am J Transplant. 2008;8:133-143.
  65. Stegall MD, Dean PG, Gloor J. Mechanisms of alloantibody production in sensitized renal allograft recipients. Am J Transplant. 2009;9:998-1005.
  66. Moreno Gonzales MA, Gandhi MJ, Schinstock CA, et al. 32 Doses of Bortezomib for Desensitization Is Not Well Tolerated and Is Associated With Only Modest Reductions in Anti-HLA Antibody. Transplantation. 2017;101:1222-1227.
  67. Liu CL, Lyle MJ, Shin SC, Miao CH. Strategies to target long-lived plasma cells for treating hemophilia A inhibitors. Cell Immunol. 2016;301:65-73.
  68. Doshi BS, Rana J, Castaman G, et al. B cell-activating factor modulates the factor VIII immune response in hemophilia A. J Clin Invest. 2021;131.
  69. Collins PW, Mathias M, Hanley J, et al. Rituximab and immune tolerance in severe hemophilia A: a consecutive national cohort. J Thromb Haemost. 2009;7:787-794.
  70. Leissinger C, Josephson C, Granger S, et al. Rituximab for treatment of inhibitors in haemophilia A. A Phase II study. Thromb Haemost. 2014;112:445-458.
  71. Bu DX, Singh R, Choi EE, et al. Pre-clinical validation of B cell maturation antigen (BCMA) as a target for T cell immunotherapy of multiple myeloma. Oncotarget. 2018;9:25764-25780.
  72. O'Connor BP, Raman VS, Erickson LD, et al. BCMA is essential for the survival of long-lived bone marrow plasma cells. J Exp Med. 2004;199:91-98.
  73. Schiemann B, et al. An essential role for BAFF in the normal development of B cells through a BCMA-independent pathway. Science. 2001;293:2111-2114.
  74. Xu S, Lam KP. B-cell maturation protein, which binds the tumor necrosis factor family members BAFF and APRIL, is dispensable for humoral immune responses. Mol Cell Biol. 2001;21:4067-4074.
  75. Barone F, Patel P, Sanderson JD, Spencer J. Gut-associated lymphoid tissue contains the molecular machinery to support T-cell-dependent and T-cell-independent class switch recombination. Mucosal Immunol. 2009;2:495-503.
  76. Carpenter RO, Evbuomwan MO, Pittaluga S, et al. B-cell maturation antigen is a promising target for adoptive T-cell therapy of multiple myeloma. Clin Cancer Res. 2013;19:2048-2060.
  77. Gustafson CE, Higbee D, Yeckes AR, et al. Limited expression of APRIL and its receptors prior to intestinal IgA plasma cell development during human infancy. Mucosal Immunol. 2014;7:467-477.
  78. Darce JR, Arendt BK, Wu X, Jelinek DF. Regulated expression of BAFF-binding receptors during human B cell differentiation. J Immunol. 2007;179:7276-7286.
  79. Brudno JN, Maric I, Hartman SD, et al. T Cells Genetically Modified to Express an Anti-B-Cell Maturation Antigen Chimeric Antigen Receptor Cause Remissions of Poor-Prognosis Relapsed Multiple Myeloma. J Clin Oncol. 2018;36:2267-2280.
  80. Walti CS, et al. Antibodies against vaccine-preventable infections after CAR-T cell therapy for B cell malignancies. JCI. Insight. 2021;6.
  81. Xu GJ, Kula T, Xu Q, et al. Viral immunology. Comprehensive serological profiling of human populations using a synthetic human virome. Science. 2015;348(6239):aaa0698
  82. Liu F, Zhang H, Wang X, et al. First-in-Human Trial of Bcma-CD19 Compound CAR with Remarkable Donor-Specific Antibody Reduction. Blood. 2019;134(1):38.
  83. Laurent SA, Hoffmann FS, Kuhn PH, et al. gamma-Secretase directly sheds the survival receptor BCMA from plasma cells. Nat Commun. 2015;6:7333.
  84. Pont MJ, Hill T, Cole GO, et al. gamma-Secretase inhibition increases efficacy of BCMA-specific chimeric antigen receptor T cells in multiple myeloma. Blood. 2019;134:1585-1597.
  85. Samur MK, Fulciniti M, Aktas Samur A, et al. Biallelic loss of BCMA as a resistance mechanism to CAR T cell therapy in a patient with multiple myeloma. Nat Commun. 2021;12:868.
  86. Fillatreau S. Regulatory functions of B cells and regulatory plasma cells. Biomed J. 2019;42:233-242.
  87. Lino AC, Dang VD, Lampropoulou V et al. LAG-3 Inhibitory Receptor Expression Identifies Immunosuppressive Natural Regulatory Plasma Cells. Immunity. 2018;49(120-133):e129.
  88. Nguyen DC, Garimalla S, Xiao H, et al. Factors of the bone marrow microniche that support human plasma cell survival and immunoglobulin secretion. Nat Commun. 2018;9:3698.
  89. Liu YN, Yang JF, Huang DJ, et al. Hypoxia Induces Mitochondrial Defect That Promotes T Cell Exhaustion in Tumor Microenvironment Through MYC-Regulated Pathways. Front Immunol. 2020;11:1906.
  90. Trudel S, Lendvai N, Popat R, et al. Targeting B-cell maturation antigen with GSK2857916 antibody-drug conjugate in relapsed or refractory multiple myeloma (BMA117159): a dose escalation and expansion phase 1 trial. Lancet Oncol. 2018;19:1641-1653.
  91. Lee HC, Raje NS, Landgren O, et al. Phase 1 study of the anti-BCMA antibody-drug conjugate AMG 224 in patients with relapsed/refractory multiple myeloma. Leukemia. 2021;35:255-258.
  92. Topp MS, Duell J, Zugmaier G, et al. Anti-B-Cell Maturation Antigen BiTE Molecule AMG 420 Induces Responses in Multiple Myeloma. J Clin Oncol. 2020;38:775-783.
  93. Malavasi F, Deaglio S, Funaro A, et al. Evolution and function of the ADP ribosyl cyclase/CD38 gene family in physiology and pathology. Physiol Rev. 2008;88:841-886.
  94. Glaría E, Valledor AF. Roles of CD38 in the Immune Response to Infection. Cells. 2020;9(1):228.
  95. Hogan KA, Chini CCS, Chini EN. The Multi-faceted Ecto-enzyme CD38: Roles in Immunomodulation, Cancer, Aging, and Metabolic Diseases. Front Immunol. 2019;10:1187.
  96. van de Donk NWCJ, Richardson PG, Malavasi F. CD38 antibodies in multiple myeloma: back to the future. Blood. 2018;131:13-29.
  97. Sanchez L, Wang Y, Siegel DS, Wang ML. Daratumumab: a first-in-class CD38 monoclonal antibody for the treatment of multiple myeloma. J Hematol Oncol. 2016;9:51.
  98. Moreau P, et al. Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial. Lancet. 2021;397(10292):2361-2371.
  99. Frerichs KA, et al. Effect of daratumumab on normal plasma cells, polyclonal immunoglobulin levels, and vaccination responses in extensively pre-treated multiple myeloma patients. Haematologica. 2020;105:e302-e306.
  100. Blankestijn MA, van de Donk NWCJ, Sasser K, Knulst AC, Otten HG. Could daratumumab be used to treat severe allergy? Journal of Allergy and Clinical Immunology. 2017;139(5):1677-1678.e3.
  101. Moonla C, Uaprasert N, Watanaboonyongcharoen P, et al. Daratumumab rapidly reduces high-titre factor VIII inhibitors in haemophilia A patients during life-threatening haemorrhages. Haemophilia. 2021;27:e155-e159.
  102. Spica D, Junker T, Dickenmann M, et al. Daratumumab for Treatment of Antibody-Mediated Rejection after ABO-Incompatible Kidney Transplantation. Case Rep Nephrol Dial. 2019;9:149-157.
  103. Pleguezuelo DE, Díaz-Simón R, Cabrera-Marante O, et al. Case Report: Resetting the Humoral Immune Response by Targeting Plasma Cells With Daratumumab in Anti-Phospholipid Syndrome. Front Immunol. 2021;12: 667515.
  104. Ostendorf L, Burns M, Durek P, et al. Targeting CD38 with Daratumumab in Refractory Systemic Lupus Erythematosus. N Engl J Med. 2020;383:1149-1155.
  105. Even-Or E, Naser Eddin A, Shadur B, et al. Successful treatment with daratumumab for post-HSCT refractory hemolytic anemia. Pediatr Blood Cancer. 2020;67(1):e28010.
  106. Scheibe F, Ostendorf L, Reincke SM, et al. Daratumumab treatment for therapy-refractory anti-CASPR2 encephalitis. J Neurol. 2020;267:317-323.
  107. Dossier C, Prim B, Moreau C, et al. A global antiB cell strategy combining obinutuzumab and daratumumab in severe pediatric nephrotic syndrome. Pediatr Nephrol. 2021;36:1175-1182.
  108. van de Donk NWCJ, Usmani SZ. CD38 Antibodies in Multiple Myeloma: Mechanisms of Action and Modes of Resistance. Frontiers in Immunology. 2018;9:2134.
  109. Nijhof IS, Casneuf T, van Velzen J, et al. CD38 expression and complement inhibitors affect response and resistance to daratumumab therapy in myeloma. Blood. 2016;128:959-970.
  110. Choudhry P, Mariano MC, Geng H, et al. DNA methyltransferase inhibitors upregulate CD38 protein expression and enhance daratumumab efficacy in multiple myeloma. Leukemia. 2020;34:938-941.
  111. Ogiya D, Liu J, Ohguchi H, et al. The JAK-STAT pathway regulates CD38 on myeloma cells in the bone marrow microenvironment: therapeutic implications. Blood. 2020;136:2334-2345.
  112. Nijhof IS, Groen RWJ, Lokhorst HM, et al. Upregulation of CD38 expression on multiple myeloma cells by all-trans retinoic acid improves the efficacy of daratumumab. Leukemia. 2015;29:2039-2049.
  113. Guo Y, Feng K, Tong C, et al. Efficiency and side effects of anti-CD38 CAR T cells in an adult patient with relapsed B-ALL after failure of bi-specific CD19/CD22 CAR T cell treatment. Cell Mol Immunol. 2020;17:430-432.
  114. Gurney M, Stikvoort A, Nolan E, et al. CD38 knockout natural killer cells expressing an affinity optimized CD38 chimeric antigen receptor successfully target acute myeloid leukemia with reduced effector cell fratricide. Haematologica. 2020.
  115. Hambach J, Riecken K, Cichutek S, et al. Targeting CD38-Expressing Multiple Myeloma and Burkitt Lymphoma Cells In Vitro with Nanobody-Based Chimeric Antigen Receptors (Nb-CARs). Cells. 2020;9.
  116. de Weers M, Tai YT, van der Veer MS, et al. Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors. J Immunol. 2011;186(3):1840-1848.
  117. Rodríguez-Lobato LG, Ganzetti M, Fernández de Larrea C, Hudecek M, Einsele H, Danhof S. CAR T-Cells in Multiple Myeloma: State of the Art and Future Directions. Frontiers in Oncology. 2020;10
  118. Pillai V, Muralidharan K, Meng W, et al. CAR T-cell therapy is effective for CD19-dim B-lymphoblastic leukemia but is impacted by prior blinatumomab therapy. Blood Adv. 2019;3:3539-3549.
  119. Liu X, Jiang S, Fang C, et al. Affinity-Tuned ErbB2 or EGFR Chimeric Antigen Receptor T Cells Exhibit an Increased Therapeutic Index against Tumors in Mice. Cancer Res. 2015;75:3596-3607.
  120. Soekojo CY, Ooi M, de Mel S, Chng WJ. Immunotherapy in Multiple Myeloma. Cells. 2020;9(3):601.
  121. Cohen AD. Myeloma: next generation immunotherapy. Hematology Am Soc Hematol Educ Program. 2019;2019:266-272.
  122. Boles KS, Nakajima H, Colonna M, et al. Molecular characterization of a novel human natural killer cell receptor homologous to mouse 2B4. Tissue Antigens. 1999;54:27-34.
  123. Bouchon A, Cella M, Grierson HL, Cohen JI, Colonna M. Activation of NK cell-mediated cytotoxicity by a SAP-independent receptor of the CD2 family. J Immunol. 2001;167:5517-5521.
  124. Campbell KS, Cohen AD, Pazina T. Mechanisms of NK Cell Activation and Clinical Activity of the Therapeutic SLAMF7 Antibody. Elotuzumab in Multiple Myeloma. Front Immunol. 2018;9:2551.
  125. O'Connell P, Pepelyayeva Y, Blake MK, et al. SLAMF7 Is a Critical Negative Regulator of IFN-alpha-Mediated CXCL10 Production in Chronic HIV Infection. J Immunol. 2019;202:228-238.
  126. O’Connell P, Hyslop S, Blake MK, Godbehere S, Amalfitano A, Aldhamen YA. SLAMF7 Signaling Reprograms T Cells toward Exhaustion in the Tumor Microenvironment. J Immunol. 2021;206(1):193-205.
  127. Chen J, Zhong MC, Guo H, et al. SLAMF7 is critical for phagocytosis of haematopoietic tumour cells via Mac-1 integrin. Nature. 2017;544(7651):493-497.
  128. von Wenserski L, Schultheiß C, Bolz S, et al. SLAMF receptors negatively regulate B cell receptor signaling in chronic lymphocytic leukemia via recruitment of prohibitin-2. Leukemia. 2021;35(4):1073-1086.
  129. Kim JR, Mathew SO, Mathew PA. Blimp-1/PRDM1 regulates the transcription of human CS1 (SLAMF7) gene in NK and B cells. Immunobiology. 2016;221:31-39.
  130. Lee JK, Mathew SO, Vaidya SV, Kumaresan PR, Mathew PA. CS1 (CRACC, CD319) induces proliferation and autocrine cytokine expression on human B lymphocytes. J Immunol. 2007;179:4672-4678.
  131. Tai YT, Dillon M, Song W, et al. Anti-CS1 humanized monoclonal antibody HuLuc63 inhibits myeloma cell adhesion and induces antibody-dependent cellular cytotoxicity in the bone marrow milieu. Blood. 2008;112:1329-1337.
  132. Tai YT, Soydan E, Song W, et al. CS1 promotes multiple myeloma cell adhesion, clonogenic growth, and tumorigenicity via c-maf-mediated interactions with bone marrow stromal cells. Blood. 2009;113:4309-4318.
  133. Lonial S, Dimopoulos M, Palumbo A, et al. Elotuzumab Therapy for Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2015;373:621-631.
  134. Vij R, Nath R, Afar DEH, et al. First-in-Human Phase I Study of ABBV-838, an Antibody-Drug Conjugate Targeting SLAMF7/CS1 in Patients with Relapsed and Refractory Multiple Myeloma. Clin Cancer Res. 2020;26:2308-2317.
  135. Lum LG, Thakur A, Elhakiem A, Alameer L, Dinning E, Huang M. Anti-CS1 x Anti-CD3 Bispecific Antibody (BiAb)-Armed Anti-CD3 Activated T Cells (CS1-BATs) Kill CS1(+) Myeloma Cells and Release Type-1 Cytokines. Front Oncol. 2020;10:544.
  136. Chan WK, Kang S, Youssef Y, et al. A CS1-NKG2D Bispecific Antibody Collectively Activates Cytolytic Immune Cells against Multiple Myeloma. Cancer Immunol Res. 2018;6:776-787.
  137. Prommersberger S, Reiser M, Beckmann J, et al. CARAMBA: a first-in-human clinical trial with SLAMF7 CAR-T cells prepared by virus-free Sleeping Beauty gene transfer to treat multiple myeloma. Gene Ther. 2021.
  138. Yan Z, Cao J, Cheng H, et al. A combination of humanised anti-CD19 and anti-BCMA CAR T cells in patients with relapsed or refractory multiple myeloma: a single-arm, phase 2 trial. Lancet Haematol. 2019;6:e521-e529.
  139. van der Schans JJ, van de Donk NWCJ, Mutis T. Dual Targeting to Overcome Current Challenges in Multiple Myeloma CAR T-Cell Treatment. Front Oncol. 2020;10:1362.
  140. Fernández de Larrea C, Staehr M, Lopez AV, et al. Defining an Optimal Dual-Targeted CAR T-cell Therapy Approach Simultaneously Targeting BCMA and GPRC5D to Prevent BCMA Escape-Driven Relapse in Multiple Myeloma. Blood Cancer Discov. 2020;1(2):146-154.
  141. Zah E, Nam E, Bhuvan V, et al. Systematically optimized BCMA/CS1 bispecific CAR-T cells robustly control heterogeneous multiple myeloma. Nat Commun. 2020;11:2283.
  142. Shalapour S, Font-Burgada J, Di Caro G, et al. Immunosuppressive plasma cells impede T-cell-dependent immunogenic chemotherapy. Nature. 2015;521:94-98.
  143. Fionda C, Abruzzese MP, Zingoni A, et al. Nitric oxide donors increase PVR/CD155 DNAM-1 ligand expression in multiple myeloma cells: role of DNA damage response activation. BMC Cancer. 2015;15:17.
  144. Guillerey C, Harjunpää H, Carrié N, et al. TIGIT immune checkpoint blockade restores CD8(+) T-cell immunity against multiple myeloma. Blood. 2018;132:1689-1694.
  145. Bezman NA, Jhatakia A, Kearney AY, et al. PD-1 blockade enhances elotuzumab efficacy in mouse tumor models. Blood Adv. 2017;1:753-765.
  146. Jelinek T, Paiva B, Hajek R. Update on PD-1/PD-L1 Inhibitors in Multiple Myeloma. Front Immunol. 2018;9:2431.
  147. Lindquist RL, Niesner RA, Hauser AE. In the Right Place, at the Right Time: Spatiotemporal Conditions Determining Plasma Cell Survival and Function. Front Immunol. 2019;10:788.
  148. Tokoyoda K, Egawa T, Sugiyama T, Choi BI, Nagasawa T. Cellular niches controlling B lymphocyte behavior within bone marrow during development. Immunity. 2004;20:707-718.
  149. Sugiyama T, Kohara H, Noda M, Nagasawa T. Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches. Immunity. 2006;25:977-988.
  150. Moore N, Moreno Gonzales M, Bonner K, Smith B, Park W, Stegall M. Impact of CXCR4/CXCL12 Blockade on Normal Plasma Cells In Vivo. Am J Transplant. 2017;17:1663-1669.
  151. Glatman Zaretsky A, Konradt C, Dépis F, et al. T Regulatory Cells Support Plasma Cell Populations in the Bone Marrow. Cell Rep. 2017;18:1906-1916.
  152. Shahabi V, Berman D, Chasalow SD, et al. Gene expression profiling of whole blood in ipilimumab-treated patients for identification of potential biomarkers of immune-related gastrointestinal adverse events. J Transl Med. 2013;11:75.
  153. Sharma A, Subudhi SK, Blando J, et al. Anti-CTLA-4 Immunotherapy Does Not Deplete FOXP3(+) Regulatory T Cells (Tregs) in Human Cancers. Clin Cancer Res. 2019;25:1233-1238.
  154. Du X, Tang F, Liu M, et al. A reappraisal of CTLA-4 checkpoint blockade in cancer immunotherapy. Cell Res. 2018;28(4):416-432.
  155. Selby MJ, Engelhardt JJ, Quigley M, et al. Anti-CTLA-4 antibodies of IgG2a isotype enhance antitumor activity through reduction of intratumoral regulatory T cells. Cancer Immunol Res. 2013;1:32-42.
  156. Bulliard Y, Jolicoeur R, Windman M, et al. Activating Fc gamma receptors contribute to the antitumor activities of immunoregulatory receptor-targeting antibodies. J Exp Med. 2013;210:1685-1693.
  157. Jang E, Cho WS, Cho ML, et al. Foxp3+ regulatory T cells control humoral autoimmunity by suppressing the development of long-lived plasma cells. J Immunol. 2011;186:1546-1553.
  158. Abdeladhim M, Zhang AH, Kropp LE, et al. Engineered ovalbumin-expressing regulatory T cells protect against anaphylaxis in ovalbumin-sensitized mice. Clin Immunol. 2019;207:49-54.
  159. Manz R, Assenmacher M, Pfluger E, Miltenyi S, Radbruch A. Analysis and sorting of live cells according to secreted molecules, relocated to a cell-surface affinity matrix. Proc Natl Acad Sci U S A. 1995;92:1921-1925.
  160. Taddeo A, Gerl V, Hoyer BF, et al. Selection and depletion of plasma cells based on the specificity of the secreted antibody. Eur J Immunol. 2015;45:317-319.
  161. Cheng Q, Pelz A, Taddeo A, et al. Selective depletion of plasma cells in vivo based on the specificity of their secreted antibodies. Eur J Immunol. 2020;50:284-291.
  162. Fraietta JA, Lacey SF, Orlando EJ, et al. Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia. Nat Med. 2018;24:563-571.
  163. Brandt LJB, Barnkob MB, Michaels YS, Heiselberg J, Barington T. Emerging Approaches for Regulation and Control of CAR T Cells: A Mini Review. Front Immunol. 2020;11:326.
  164. Di Stasi A, Tey SK, Dotti G, et al. Inducible apoptosis as a safety switch for adoptive cell therapy. N Engl J Med. 2011;365:1673-1683.
  165. Yu S, Yi M, Qin S, Wu K. Next generation chimeric antigen receptor T cells: safety strategies to overcome toxicity. Mol Cancer. 2019;18:125.
  166. Brink R. Regulation of B cell self-tolerance by BAFF. Semin Immunol. 2006;18:276-283.
  167. Cancro MP, D'Cruz DP, Khamashta MA. The role of B lymphocyte stimulator (BLyS) in systemic lupus erythematosus. J Clin Invest. 2009;119:1066-1073.
  168. Wardemann H, Nussenzweig MC. B-cell self-tolerance in humans. Adv Immunol. 2007;95:83-110.
  169. Amanna IJ, Dingwall JP, Hayes CE. Enforced bcl-xL gene expression restored splenic B lymphocyte development in BAFF-R mutant mice. J Immunol. 2003;170:4593-4600.
  170. Schweighoffer E, Vanes L, Nys J, et al. The BAFF receptor transduces survival signals by co-opting the B cell receptor signaling pathway. Immunity. 2013;38:475-488.
  171. Hase H, Kanno Y, Kojima M, et al. BAFF/BLyS can potentiate B-cell selection with the B-cell coreceptor complex. Blood. 2004;103:2257-2265.
  172. Smith SH, Cancro MP. Cutting edge: B cell receptor signals regulate BLyS receptor levels in mature B cells and their immediate progenitors. J Immunol. 2003;170:5820-5823.
  173. Khan WN. B cell receptor and BAFF receptor signaling regulation of B cell homeostasis. J Immunol. 2009;183:3561-3567.
  174. Lavie F, Miceli-Richard C, Ittah M, Sellam J, Gottenberg JE, Mariette X. Increase of B cell-activating factor of the TNF family (BAFF) after rituximab treatment: insights into a new regulating system of BAFF production. Ann Rheum Dis. 2007;66:700-703.

MeSH Term

Antibody-Producing Cells
Autoimmunity
B-Lymphocytes
Immunity, Humoral
Plasma Cells
Journal Article Research Support, Non-U.S. Gov't Review
Article has an altmetric score of 2

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