Tabelle 1
Therapeutische monoklonale Antikörper, Fusionsproteine und CAR-(Chimeric Antigen Receptor-)transduzierte T-Zellen mit dem Potential B- und Plasmazellen direkt oder indirekt
zu hemmen.
name / Type of monoclonal antibody / Level of intervention / Route of
application / Registered or
off-label clinical use
Licensed indication / References
Therapeutic monoclonal antibodies
BAFF / Belimumab / Benlysta / Fully human (GSK1550188 or HGS1006) / Neutralizes soluble BAFF / iv / SLE, non-renal forms / 1. Lutalo 2014
2.Vilas-Boas 2015
3.Baker, et al 2003
4.Morais et al 2015
CD3/ CD19 / Blinatumomab / Blincyto / Bi-specific
T cell engager (BiTEs) / Links cytotoxic
T cell to malignant CD19+ B cells / iv / Acute lymphoblastic leukemia Phi neg
Blincyto is indicated for the treatment of adults with Philadelphia chromosome negative relapsed or refractory B-precursor acute lymphoblastic leukaemia (ALL) / 6. Topp et al 2011
CD20: / Rituximab / Rituxan
Mabthera
Truxima / Chimeric
Rituximab epitope / Depletes B-cells expressing the CD20 antigen;does not deplete plasma cells / iv / B-NHL,
Rheumatoid Arthritis / 13. De Angelis et al 2015
14. Edwards et al 2004
CD20: / Obinutuzumab / Gazyvaro / Humanized
Ofatumumab and Rituximab epitope / Depletes CD20 B cells / iv / chronic lymphocytic leukaemia (CLL);
superior to rituximab / 9. Owen, Stewart 2015
Anti-CD20 Ofatumumab-epitope / Ofatumumab / Arzerra / Fully human mAb / Depletes B-cells expressing the CD20 antigen / iv / Previously untreated chronic lymphocytic leukaemia (CLL) and
Refractory CLL / 10. Hillmen et al 2015
11. Österborg et al 2015
CD20: / Ocrelizumab / Humanized
Rituximab epitope / Depletes B-cells expressing CD20
Does not plasma cell / iv / Multiple sclerosis,
licence in 2016 / 12.Kappos L et al 2011
CD22
(Siglec 2) / Epratuzumab / Humanized IgG1
Anti-Siglec 2 / inhibits the production of the proinflamma-
tory cytokines IL-6 and TNF-α,but not the regulatory cytokine IL-10, by B cells / iv / SLE , Refracory aggressive B-NHL, Sjögren’s
Studies ongoing in SLE, NHL / 15. Dörner et al 2006
CD22
(Siglec 2) / Inotuzumab Ozogamicin / Humanized IgG4
Anti-siglec 2conjugated to toxic drug ozagamicin / Binds to the endocytotic receptor CD22, expressed by majority of B cells; having bound a potent DNA-binding cytotxic agent / iv / Acute B-ALL
orphan designation (EU/3/13/1127) was granted by the European Commission to Pfizer Limited, United Kingdom, for inotuzumab ozogamicin for the treatment of B-cell acute lymphoblastic leukaemia. / 16. Kantarijan et al 2013
CD25 / Daclizumab
Basiliximab (biosimilar) / Zenapax
Xenopax / Humanised IgG1 anti-IL2R achain / Blockade of IL2R and T cell activation / iv / Licensed for acute GvH Reaction in allograft recipients, Allograft rejection, MS,
Conjugated with Y90 in T cell leukemias / 18. Kappos et al 2015
CD52 / Alemtuzumab / Campath-1H
Lemtrada (for MS) / Humanized IgGκ1 anti-glycoprotein on cytotoxic T, B and NK cells.
All mononuclear cells in blood / Cytotoxicity of CD52 bearing cells / iv / Registered for CLL and MS.
Side effects: Hypo-g-globulinemia and secondary autoimmune disease (thyroid autoimmunity, immune thrombocytopenia) / 19. Ruck et al 2015
20. Willis et al 2015
21. Hartung et al 2015
Anti-IL6Ra / Tocilizumab / Ro-Actemra / Fully human / Binds soluble and membrane bound IL-6R. IL-6/IL-6R interactions are critical for B-cell differentiation and plasmablast growth and plasma cell IgG production. / Iv, sc / Rheumatoid arthritis,
Current studies use Tocilizumab in combination with IVIG for desen-sitization and to treat Still’s disease with complications. / 22. Burmester et al 2015
23. Furst et al 2011
24. Yamamoto et al 2015
Anti- FcRn / UCB7665 / Humanized IgG4 / Accelerated IgG catabolism / Iv, sc / Ongoing phase I/II studies, planned studies in autoimmune diseases.
Dose-dependent hypo-y-globulinemia / 27.Nixon et al 2015
CD40L
(CD154) / Hu5c8
IDEC-131 / Humanized IgG1 / Blocks CD40L-CD40 interaction / iv / Chronic refractory ITP / 34. Patel et al 2008
Fusion proteins and peptides
BAFF / Blisibimod / Fusion polypeptide
protein (AMG623) / Blocks soluble and membrane expressed biologically active BAFF
Clinical effect similar to the anti-BAFF Tabalumab / iv / Testing in SLE, RA, SS
and myositis / 28.Stohl et al 2015
4. Morais et al, 2015
TACI / Atacicept / TACI-Fc fusion protein (K3D9A0ICQ3) / Critical blockade of peripheral B cell development
Neutralises soluble April and BAFF and impaires B cell differntiation / iv / Ongoing studies in SLE, RA and MS
Severe hypo-g-globulinemia in SLE / 29. Nestorov et al 2008
30. Ginzler et al 2012
31. Isenberg et al 2015
4. Morais et al 2015
Chimeric antigen receptor (CAR) transduced T cells
CD19 directed / CD19-CAR transduced T cells (CTL019) / Chimeric antigen receptor T cells (CARTs) / Kills CD19 expressing ALL cells / iv / Refractory ALL , after HSCT, high remission rate / 32. Maude et al 2014
33. Lee et al 2015
*this table is not considered to be complete (as of November 22, 2015)
APRIL: A proliferation inducing ligand; a cytokine essential for B-cell proliferation and survival from the immature stages to the development of plasma cells
BAFF: B cell activating factor; a cytokine, essential for B-cell proliferation and survival from the immature stages to the development of plasma cells. BAFF-R, receptor for BAFF
JIA: juvenile idiopathic arthritis
MAb: monoclonal antibody
TACI: transmembrane activator and calcium modulator and cyclophilin ligand interactor
Referenzen zur Tabelle 1
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