TGN1412 induces lymphopenia and human cytokine release in a humanized mouse model

PLoS ONE

Volumn 11, Issue 3, 2016, Pages

  Weißmüller, Sabrina ^a   Kronhart, Stefanie ^a   Kreuz, Dorothea ^a   Schnierle, Barbara ^a   Kalinke, Ulrich ^b   Kirberg, Jörg ^a   Hanschmann, Kay Martin ^a   Waibler, Zoe ^a  

^a PAUL EHRLICH INSTITUT   (Germany)

^b INSTITUTE OF INFECTION IMMUNOLOGY   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

CD11B ANTIGEN; CD19 ANTIGEN; CD45 ANTIGEN; GAMMA INTERFERON; INTERLEUKIN 10; INTERLEUKIN 12P70; INTERLEUKIN 1BETA; INTERLEUKIN 5; INTERLEUKIN 8; OKT 3; TGN 1412; TUMOR NECROSIS FACTOR ALPHA; CYTOKINE; LEUKOCYTE ANTIGEN; MONOCLONAL ANTIBODY; TGN-1412 MONOCLONAL ANTIBODY;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BODY TEMPERATURE; CD3+ T LYMPHOCYTE; CD4 CD8 RATIO; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL LOSS; CONTROLLED STUDY; CYTOKINE RELEASE; DOWN REGULATION; DRUG SAFETY; HUMAN; HUMAN CELL; LYMPHOCYTOPENIA; MOUSE; NONHUMAN; PREDICTIVE VALUE; PROTEIN EXPRESSION; T CELL DEPLETION; T LYMPHOCYTE; ANIMAL; BLOOD; CHEMICALLY INDUCED; DRUG EFFECTS; IMMUNOLOGY; IMMUNOMODULATION; METABOLISM;

ANIMALS; ANTIBODIES, MONOCLONAL, HUMANIZED; ANTIGENS, CD; CYTOKINES; HUMANS; IMMUNOMODULATION; LYMPHOPENIA; MICE; MODELS, ANIMAL; MUROMONAB-CD3; T-LYMPHOCYTES;

EID: 84961233695     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0149093     Document Type: Article

References (44)

1. Reichert JM. Marketed therapeutic antibodies compendium. mAbs 2012; 4(3):413-5. doi: 10.4161/ mabs.19931 PMID: 22531442
2. Suntharalingam G, Perry MR, Ward S, Brett SJ, Castello-Cortes A, Brunner MD, et al. Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412. The New England journal of medicine 2006; 355(10):1018-28. PMID: 16908486
3. Abramowicz D, Schandene L, Goldman M, Crusiaux A, Vereerstraeten P, de Pauw L, et al. Release of tumor necrosis factor, interleukin-2, and gamma-interferon in serum after injection of OKT3 monoclonal antibody in kidney transplant recipients. Transplantation 1989; 47(4):606-8. PMID: 2523100
4. Horvath C, Andrews L, Baumann A, Black L, Blanset D, Cavagnaro J, et al. Storm forecasting: additional lessons from the CD28 superagonist TGN1412 trial. Nature reviews. Immunology 2012; 12 (10):740; author reply 740. doi: 10.1038/nri3192-c1 PMID: 22941443
5. Hünig T. The storm has cleared: lessons from the CD28 superagonist TGN1412 trial. Nature reviews. Immunology 2012; 12(5):317-8. doi: 10.1038/nri3192 PMID: 22487653
6. Beyersdorf N, Gaupp S, Balbach K, Schmidt J, Toyka KV, Lin C, et al. Selective targeting of regulatory T cells with CD28 superagonists allows effective therapy of experimental autoimmune encephalomyelitis. The Journal of experimental medicine 2005; 202(3):445-55. PMID: 16061730
7. Perrin PJ, June CH, Maldonado JH, Ratts RB, Racke MK. Blockade of CD28 during in vitro activation of encephalitogenic T cells or after disease onset ameliorates experimental autoimmune encephalomyelitis. Journal of immunology (Baltimore, Md.: 1950) 1999; 163(3):1704-10.
8. Hünig T. Manipulation of regulatory T-cell number and function with CD28-specific monoclonal antibodies. Advances in immunology 2007; 95:111-48. PMID: 17869612
9. Lin C, Hünig T. Efficient expansion of regulatory T cells in vitro and in vivo with a CD28 superagonist. European journal of immunology 2003; 33(3):626-38. PMID: 12616483
10. TeGenero AG. TGN1412 Investigational Medicinal Product Dossier. Available: http://www.circare.org/ foia5/TGN1412dossier.pdf2005.
11. Bugelski PJ, Achuthanandam R, Capocasale RJ, Treacy G, Bouman-Thio E. Monoclonal antibodyinduced cytokine-release syndrome. Expert review of clinical immunology 2009; 5(5):499-521. doi: 10.1586/eci.09.31 PMID: 20477639
12. FDA. Guidance for industry and reviewers; estimating the safe starting dose in clinical trials for therapeutics in adult healthy volunteers.; 2002.
13. Jannsen-Cilag. Package insert.; 2008.
14. TeGenero AG. Investigators brochure. Available: http://www.circare.org/foia5/ tgn1412investigatorbrochure.pdf.
15. Siegel SA, Shealy DJ, Nakada MT, Le J, Woulfe DS, Probert L, et al. The mouse/human chimeric monoclonal antibody cA2 neutralizes TNF in vitro and protects transgenic mice from cachexia and TNF lethality in vivo. Cytokine 1995; 7(1):15-25. PMID: 7538333
16. Büchner SM, Sliva K, Bonig H, Völker I, Waibler Z, Kirberg J, et al. Delayed onset of graft-versus-host disease in immunodeficent human leucocyte antigen-DQ8 transgenic, murine major histocompatibility complex class II-deficient mice repopulated by human peripheral blood mononuclear cells. Clinical and experimental immunology 2013; 173(2):355-64. doi: 10.1111/cei.12121 PMID: 23607364
17. Henell KR, Bakke A, Kenny TA, Kimball JA, Barry JM, Norman DJ. Degree of modulation of cell-surface CD3 by anti-lymphocyte therapies. Transplantation proceedings 1991; 23(1 Pt 2):1070-1. PMID: 1824886
18. Norman DJ. Mechanisms of action and overview of OKT3. Therapeutic drug monitoring 1995; 17 (6):615-20. PMID: 8588230
19. Chatenoud L, Baudrihaye MF, Kreis H, Goldstein G, Schindler J, Bach JF. Human in vivo antigenic modulation induced by the anti-T cell OKT3 monoclonal antibody. European journal of immunology 1982; 12(11):979-82. PMID: 6759145
20. Chatenoud L. CD3-specific antibody-induced active tolerance: from bench to bedside. Nature reviews. Immunology 2003; 3(2):123-32. PMID: 12563296
21. Henell KR, Norman DJ. Monitoring OKT3 treatment: pharmacodynamic and pharmacokinetic measures. Transplantation proceedings 1993; 25(2 Suppl 1):83-5. PMID: 8465435
22. Hudis CA. Trastuzumab - mechanism of action and use in clinical practice. The New England journal of medicine 2007; 357(1):39-51. PMID: 17611206
23. King MA, Covassin L, Brehm MA, Racki W, Pearson T, Leif J, et al. Human peripheral blood leucocyte non-obese diabetic-severe combined immunodeficiency interleukin-2 receptor gamma chain gene mouse model of xenogeneic graft-versus-host-like disease and the role of host major histocompatibility complex. Clinical and experimental immunology 2009; 157(1):104-18. doi: 10.1111/j.1365-2249.2009. 03933.x PMID: 19659776
24. Zaiss MM, Frey B, Hess A, Zwerina J, Luther J, Nimmerjahn F, et al. Regulatory T cells protect from local and systemic bone destruction in arthritis. Journal of immunology (Baltimore, Md.: 1950) 2010; 184(12):7238-46.
25. Eastwood D, Findlay L, Poole S, Bird C, Wadhwa M, Moore M, et al. Monoclonal antibody TGN1412 trial failure explained by species differences in CD28 expression on CD4+ effector memory T-cells. British journal of pharmacology 2010; 161(3):512-26. doi: 10.1111/j.1476-5381.2010.00922.x PMID: 20880392
26. Vudattu NK, Waldron-Lynch F, Truman LA, Deng S, Preston-Hurlburt P, Torres R, et al. Humanized mice as a model for aberrant responses in human T cell immunotherapy; 2014.
27. Waldron-Lynch F, Deng S, Preston-Hurlburt P, Henegariu O, Herold KC. Analysis of human biologics with a mouse skin transplant model in humanized mice; 2012.
28. Chatenoud L, Ferran C, Legendre C, Thouard I, Merite S, Reuter A, et al. In vivo cell activation following OKT3 administration. Systemic cytokine release and modulation by corticosteroids. Transplantation 1990; 49(4):697-702. PMID: 2109379
29. Waid TH, Lucas BA, Thompson JS, McKeown JW, Brown S, Kryscio R, et al. Treatment of renal allograft rejection with T10B9.1A31 or OKT3: final analysis of a phase II clinical trial. Transplantation 1997; 64(2):274-81. PMID: 9256187
30. Malcolm SL, Smith EL, Bourne T, Shaw S. A humanised mouse model of cytokine release: comparison of CD3-specific antibody fragments. Journal of immunological methods 2012; 384(1-2):33-42. doi: 10.1016/j.jim.2012.07.001 PMID: 22796190
31. Legrand N, Cupedo T, van Lent AU, Ebeli MJ, Weijer K, Hanke T, et al. Transient accumulation of human mature thymocytes and regulatory T cells with CD28 superagonist in "human immune system" Rag2(-/-)gammac(-/-) mice. Blood 2006; 108(1):238-45. PMID: 16514056
32. Müller N, van den Brandt J, Odoardi F, Tischner D, Herath J, Flügel A, et al. A CD28 superagonistic antibody elicits 2 functionally distinct waves of T cell activation in rats. The Journal of clinical investigation 2008; 118(4):1405-16. doi: 10.1172/JCI32698 PMID: 18357346
33. Terrell TG, Green JD. Comparative pathology of recombinant murine interferon-gamma in mice and recombinant human interferon-gamma in cynomolgus monkeys. International review of experimental pathology 1993; 34 Pt B:73-101. PMID: 8458720
34. Tabares P, Berr S, Römer PS, Chuvpilo S, Matskevich AA, Tyrsin D, et al. Human regulatory T cells are selectively activated by low-dose application of the CD28 superagonist TGN1412/TAB08. European journal of immunology 2014; 44(4):1225-36. doi: 10.1002/eji.201343967 PMID: 24374661
35. Bartholomaeus P, Semmler LY, Bukur T, Boisguerin V, Römer PS, Tabares P, et al. Cell contactdependent priming and Fc interaction with CD32+ immune cells contribute to the TGN1412-triggered cytokine response. Journal of immunology (Baltimore, Md.: 1950) 2014; 192(5):2091-8.
36. Stebbings R, Findlay L, Edwards C, Eastwood D, Bird C, North D, et al. "Cytokine storm" in the phase I trial of monoclonal antibody TGN1412: better understanding the causes to improve preclinical testing of immunotherapeutics. Journal of immunology (Baltimore, Md.: 1950) 2007; 179(5):3325-31.
37. Waibler Z, Sender LY, Merten C, Hartig R, Kliche S, Gunzer M, et al. Signaling signatures and functional properties of anti-human CD28 superagonistic antibodies. PloS one 2008; 3(3):e1708. doi: 10.1371/journal.pone.0001708 PMID: 18320029
38. Weissmüller S, Semmler LY, Kalinke U, Christians S, Müller-Berghaus J, Waibler Z. ICOS-LICOS interaction is critically involved in TGN1412-mediated T-cell activation. Blood 2012; 119(26):6268-77. doi: 10.1182/blood-2011-12-401083 PMID: 22577174
39. Römer PS, Berr S, Avota E, Na S, Battaglia M, Berge I ten, et al. Preculture of PBMCs at high cell density increases sensitivity of T-cell responses, revealing cytokine release by CD28 superagonist TGN1412. Blood 2011; 118(26):6772-82. doi: 10.1182/blood-2010-12-319780 PMID: 21931118
40. Smith JA, Bluestone JA. T cell inactivation and cytokine deviation promoted by anti-CD3 mAbs. Current opinion in immunology 1997; 9(5):648-54. PMID: 9368773
41. Shultz LD, Ishikawa F, Greiner DL. Humanized mice in translational biomedical research. Nature reviews. Immunology 2007; 7(2):118-30. PMID: 17259968
42. Tary-Lehmann M, Lehmann PV, Schols D, Roncarolo MG, Saxon A. Anti-SCID mouse reactivity shapes the human CD4+ T cell repertoire in hu-PBL-SCID chimeras. The Journal of experimental medicine 1994; 180(5):1817-27. PMID: 7964463
43. Blum KS, Pabst R. Lymphocyte numbers and subsets in the human blood. Do they mirror the situation in all organs? Immunology letters 2007; 108(1):45-51. PMID: 17129612
44. Smit-McBride Z, Mattapallil JJ, McChesney M, Ferrick D, Dandekar S. Gastrointestinal T lymphocytes retain high potential for cytokine responses but have severe CD4(+) T-cell depletion at all stages of simian immunodeficiency virus infection compared to peripheral lymphocytes. Journal of virology 1998; 72 (8):6646-56. PMID: 9658111