Анти-CD19-моноклональные антитела при острой лимфобластной лейкемии у детей
Аннотация
Разработка моноклональных антител для лечения гемобластозов является быстро развивающейся областью науки. Ряд соединений оказался эффективен при лечении острого лимфобластного лейкоза (ОЛЛ) у детей. В то время как неконъюгированные гуманизированные антитела хорошо переносимы и могут быть легко объединены с химиотерапией, иммуноконъюгаты, доставляющие токсические соединения прямо в клетки-мишени, имеют более серьезные побочные эффекты. Антигены с высокой и селективной экспрессией являются идеальными мишенями для использования антител и подходят для исследований фазы I/II и III при ОЛЛ у детей. Антигены, стабильно экспрессирующиеся на поверхности клетки, подходят как для неконъюгированных антител, вызывающих антитело-зависимую клеточную и комплемент-зависимую цитотоксичность, так и для биспецифических антител с участием Т-клеток. Моноклональные антитела обладают совершенно иным механизмом действия по сравнению с таковым обычной химиотерапии и, безусловно, способны существенно изменить стратегию лечения ОЛЛ в будущем.
Об авторах
А. И. Карачунский
ФГБУ «ФНКЦ ДГОИ им. Дмитрия Рогачева» Минздрава России;
Россия
117997, Москва, ул. Саморы Машела, 1
Россия
117997, Москва, ул. Саморы Машела, 1
Ю. В. Румянцева
ФГБУ «ФНКЦ ДГОИ им. Дмитрия Рогачева» Минздрава России;
Россия
117997, Москва, ул. Саморы Машела, 1
Россия
117997, Москва, ул. Саморы Машела, 1
А. фон Штакельберг
Университетская клиника педиатрии, специализирующаяся в онкологии и гематологии, Университетского медицинского комплекса Шарите
Германия
Берлин
Германия
Берлин
Список литературы
1. Kohler G., Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 1975;256:495–7.
2. Riechmann L., Clark M., Waldmann H., Winter G. Reshaping human antibodies for therapy. Nature 1988;332:323–7.
3. Lazar G.A., Desjarlais J.R., Jacinto J. et al. A molecular immunology approach to antibody humanization and functional optimization. Mol Immunol 2007;44:1986–98.
4. Kreitman R.J. Recombinant immunotoxins containing truncated bacterial toxins for the treatment of hematologic malignancies. Bio Drugs 2009;23:1–13.
5. Du X., Beers R., Fitzgerald D.J., Pastan I. Differential cellular internalization of antiCD19 and -CD22 immunotoxins results in different cytotoxic activity. Cancer Res 2008;68:6300–5.
6. Sapra P., Allen T.M. Internalizing antibodies are necessary for improved therapeutic efficacy of antibody-targeted liposomal drugs. Cancer Res 2002;62:7190–4.
7. Labrijn A.F., Aalberse R.C., Schuurman J. When binding is enough: nonactivating antibody formats. Curr Opin Immunol 2008;20:479–85.
8. Gudowius S., Recker K., Laws H.J. et al. Identification of candidate target antigens for antibody-based immunotherapy in childhood B-cell precursor ALL. Klin Padiatr 2006;218:327–33.
9. Bene M.C. Immunophenotyping of acute leukaemias. Immunol Lett 2005;98:9–21.
10. Preijers F.W., Tax W.J., De Witte T. et al. Relationship between internalization and cytotoxicity of ricin A-chain immunotoxins. Br J Haematol 1988;70:289–94.
11. Desjarlais J.R., Lazar G.A., Zhukovsky E.A., Chu S.Y. Optimizing engagement of the immune system by anti-tumor antibodies: an engineer's perspective. Drug Discov Today 2007;12:898–910.
12. van Mirre E., Breunis W.B., Geissler J. et al. Neutrophil responsiveness to IgG, as determined by fixed ratios of mRNA levels for activating and inhibitory FcgammaRII (CD32), is stable over time and unaffected by cytokines. Blood 2006;108:584–90.
13. Pricop L., Redecha P., Teillaud J.L. et al. Differential modulation of stimulatory and inhibitory Fc gamma receptors on human monocytes by Th1 and Th2 cytokines. J Immunol 2001;166:531–7.
14. Dranoff G. Cytokines in cancer pathogenesis and cancer therapy. Nat Rev Cancer 2004;4:11–22.
15. Kashii Y., Giorda R., Herberman R.B. et al. Constitutive expression and role of the TNF family ligands in apoptotic killing of tumor cells by human NK cells. J Immunol 1999;163:5358–66.
16. Boruchov A.M., Heller G., Veri M.C. et al. Activating and inhibitory IgG Fc receptors on human DCs mediate opposing functions. J Clin Invest 2005;115:2914–23.
17. Michon J.M., Gey A., Moutel S. et al. In vivo induction of functional Fc gammaRI (CD64) on neutrophils and modulation of blood cytokine mRNA levels in cancer patients treated with G-CSF (rMetHuG-CSF). Br J Haematol 1998;100:550–6.
18. Rech J., Repp R., Rech D. et al. A humanized HLA-DR antibody (hu1D10, apolizumab) in combination with granulocyte colony-stimulating factor (filgrastim) for the treatment of non-Hodgkin's lymphoma: a pilot study. Leuk Lymphoma 2006;47:2147–54.
19. Dechant M., Bruenke J., Valerius T. HLA class II antibodies in the treatment of hematologic malignancies. Semin Oncol 2003;30:465–75.
20. Selenko N., Majdic O., Jager U. et al. Crosspriming of cytotoxic T cells promoted by apoptosis-inducing tumor cell reactive antibodies? J Clin Immunol 2002;22:124–30.
21. Selenko N., Maidic O., Draxier S. et al. CD20 antibody (C2B8)-induced apoptosis of lymphoma cells promotes phagocytosis by dendritic cells and cross-priming of CD8+cytotoxic T cells. Leukemia 2001;15:1619–26.
22. Idusogie E.E., Wong P.Y., Presta L.G. et al. Engineered antibodies with increased activity to recruit complement. J Immunol 2001;166:2571–5.
23. Dall’Acqua W.F., Cook K.E., Damschroder M.M. et al. Modulation of the effector functions of a human IgG1 through engineering of its hinge region. J Immunol 2006;177:1129–38.
24. Nimmerjahn F., Ravetch J.V. Divergent immunoglobulin g subclass activity through selective Fc receptor binding. Science 2005;310:1510–2.
25. Richards J.O., Karki S., Lazar G.A. et al. Optimization of antibody binding to FcgammaRIIa enhances macrophage phagocytosis of tumor cells. Mol Cancer Ther 2008;7:2517–27.
26. Lazar G.A., Dang W., Karki S. et al. Engineered antibody Fc variants with enhanced effector function. Proc Natl Acad Sci USA 2006;103:4005–10.
27. Bowles J.A., Wang S.Y., Link B.K. et al. Anti-CD20 monoclonal antibody with enhanced affinity for CD16 activates NK cells at lower concentrations and more effectively than rituximab. Blood 2006;108:2648–54.
28. Kufer P., Lutterbuse R., Baeuerle P.A. A revival of bispecific antibodies. Trends Biotechnol 2004;22:238–44.
29. Offner S., Hofmeister R., Romaniuk A. et al. Induction of regular cytolytic T cell synapses by bispecific single-chain antibody constructs on MHC class I-negative tumor cells. Mol Immunol 2006;43:763–71.
30. Bargou R., Leo E., Zugmaier G. et al. Tumor regression in cancer patients by very low doses of a T cell-engaging antibody. Science 2008;321:974–7.
31. Loffler A., Kufer P., Lutterbuse R. et al. A recombinant bispecific single-chain antibody, CD19 × CD3, induces rapid and high lymphoma-directed cytotoxicity by unstimulated T lymphocytes. Blood 2000;95:2098–103.
32. Vallera D.A., Todhunter D.A., Kuroki D.W. et al. A bispecific recombinant immunotoxin, DT2219, targeting human CD19 and CD22 receptors in a mouse xenograft model of B-cell leukemia/lymphoma. Clin Cancer Res 2005;11:3879–88.
33. WHO Expert Committee on Specifications for Pharmaceutical Preparations. World Health Organ Tech Rep Ser 2008:1–138.
34. Uckun F.M., Kersey J.H., Haake R. et al. Autologous bone marrow transplantation in high-risk remission B-lineage acute lymphoblastic leukemia using a cocktail of three monoclonal antibodies (BA-1/CD24, BA-2/CD9, and BA-3/CD10) plus complement and 4-hydroperoxycyclophosphamide for ex vivo bone marrow purging. Blood 1992;79:1094–104.
35. Hasegawa M., Fujimoto M., Poe J.C. et al. CD19 can regulate B lymphocyte signal transduction independent of complement activation. J Immunol 2001;167:3190–200.
36. Horton H.M., Bernett M.J., Pong E. et al. Potent in vitro and in vivo activity of an Fcengineered anti-CD19 monoclonal antibody against lymphoma and leukemia. Cancer Res 2008;68:8049–57.
37. Anderson K.C., Bates M.P., Slaughenhoupt B.L. et al. Expression of human B cellassociated antigens on leukemias and lymphomas: a model of human B cell differentiation. Blood 1984;63:1424–33.
38. Uckun F.M., Jaszcz W., Ambrus J.L. et al. Detailed studies on expression and function of CD19 surface determinant by using B43 monoclonal antibody and the clinical potential of anti-CD19 immunotoxins. Blood 1988;71:13–29.
39. Tedder T.F., Inaoki M., Sato S. The CD19-CD21 complex regulates signal transduction thresholds governing humoral immunity and autoimmunity. Immunity 1997;6:107–18.
40. Yazawa N., Hamaguchi Y., Poe J.C., Tedder T.F. Immunotherapy using unconjugated CD19 monoclonal antibodies in animal models for B lymphocyte malignancies and autoimmune disease. Proc Natl Acad Sci USA 2005;102:15178–83.
41. Vlasveld L.T., Hekman A., Vyth-Dreese F.A. et al. Treatment of low-grade non-Hodgkin’s lymphoma with continuous infusion of low-dose recombinant interleukin-2 in combination with the B-cell-specific monoclonal antibody CLBCD19. Cancer Immunol Immunother 1995;40:37–47.
42. Hekman A., Honselaar A., Vuist W.M. et al. Initial experience with treatment of human B cell lymphoma with anti-CD19 monoclonal antibody. Cancer Immunol Immunother 1991;32:364–72.
43. Grossbard M.L., Lambert J.M., Goldmacher V.S. et al. Anti-B4-blocked ricin: a phase I trial of 7-day continuous infusion in patients with B-cell neoplasms. J Clin Oncol 1993;11:726–37.
44. Multani P.S., O’Day S., Nadler L.M., Grossbard M.L. Phase II clinical trial of bolus infusion anti-B4 blocked ricin immunoconjugate in patients with relapsed Bcell non-Hodgkin’s lymphoma. Clin Cancer Res 1998;4:2599–604.
45. Rowland A.J., Pietersz G.A., McKenzie I.F. Preclinical investigation of the antitumour effects of anti-CD19-idarubicin immunoconjugates. Cancer Immunol Immunother 1993;37:195–202.
46. Sapra P., Allen T.M. Improved outcome when B-cell lymphoma is treated with combinations of immunoliposomal anticancer drugs targeted to both the CD19 and CD20 epitopes. Clin Cancer Res 2004;10:2530–7.
47. Schwemmlein M., Stieglmaier J., Kellner C. et al. A CD19-specific single-chain immunotoxin mediates potent apoptosis of B-lineage leukemic cells. Leukemia 2007;21:1405–12.
48. Ingle G.S., Chan P., Elliott J.M. et al. High CD21 expression inhibits internalization of antiCD19 antibodies and cytotoxicity of an antiCD19-drug conjugate. Br J Haematol 2008;140:46–58.
49. Gerber H.P., Kung-Sutherland M., Stone I. et al. Potent antitumor activity of the anti-CD19 auristatin antibody drug conjugate hBU12-vcMMAE against rituximab-sensitive and -resistant lymphomas. Blood 2009;113:4352–61.
50. Stieglmaier J., Bremer E., Kellner C. et al. Selective induction of apoptosis in leukemic Blymphoid cells by a CD19-specific TRAIL fusion protein. Cancer Immunol Immunother 2008;57:233–46.
51. Molhoj M., Crommer S., Brischwein K. et al. CD19-/CD3-bispecific antibody of the BiTE class is far superior to tandem diabody with respect to redirected tumor cell lysis. Mol Immunol 2007;44:1935–43.
52. Brandl C., Haas C., d’Argouges S. et al. The effect of dexamethasone on polyclonal T cell activation and redirected target cell lysis as induced by a CD19/CD3-bispecific singlechain antibody construct. Cancer Immunol Immunother 2007;56:1551–63.
53. d’Argouges S., Wissing S., Brandl C. et al. Combination of rituximab with blinatumomab (MT103/MEDI-538), a T cell-engaging CD19-/CD3-bispecific antibody, for highly efficient lysis of human B lymphoma cells. Leuk Res 2009;33:465–73.
54. Topp M., Goekbuget N., Kufer P. et al. Treatment with Anti-CD19 BiTE Antibody Blinatumomab (MT103 / MEDI-538) Is Able to Eliminate Minimal Residual Disease (MRD) in Patients with B-Precursor Acute Lymphoblastic Leukemia (ALL): First Results of An Ongoing Phase II Study. ASH Annual Meeting Abstracts 2008;112:1926.
55. Kellner C., Bruenke J., Stieglmaier J. et al. A novel CD19-directed recombinant bispecific antibody derivative with enhanced immune effector functions for human leukemic cells. J Immunother 2008;31:871–84.
56. Hoffmann P., Hofmeister R., Brischwein K. et al. Serial killing of tumor cells by cytotoxic T cells redirected with a CD19-/ CD3-bispecific single-chain antibody construct. Int J Cancer 2005;115:98–104.
57. Portell C.A., Wenzell C.M., Advani A.S. Clinical and pharmacologic aspects of blinatumomab in the treatment of B- cell acute lymphoblastic leukemia. Clin Pharmacol 2013;5:5–11.
58. http://tabs.craic.com/. antibodies. Theraputic antibody database 2015.
59. Golay J., D’Amico A., Borleri G. et al. A novel method using blinatumomab for efficient, clinical-grade expansion of polyclonal T cells for adoptive immunotherapy. J Immunol 2014;193:4739–47.
60. Klinger M., Brandl C., Zugmaier G. et al. Immunopharmacologic response of patients with B-lineage acute lymphoblastic leukemia to continuous infusion of T cell- engaging CD19/CD3-bispecific BiTE antibody blinatumomab. Blood 2012;119:6226–33.
61. Schlegel P., Lang P., Zugmaier G. et al. Pediatric posttransplant relapsed/refractory Bprecursor acute lymphoblastic leukemia shows durable remission by therapy with the T-cell engaging bispecific antibody blinatumomab. Haematologica 2014;99:1212–9.
62. Topp M.S., Kufer P., Gökbuget N. et al. Targeted therapy with the T-cell-engaging antibody blinatumomab of chemotherapyrefractory minimal residual disease in Blineage acute lymphoblastic leukemia patients results in high response rate and prolonged leukemia-free survival. J Clin Oncol 2011;29:2493–8.
63. Bassan R., Dell’Angelo O., Paolo G.E. Toward victory in adult ALL: blinatumomab joins in. Blood 2012;120:5094–5.
64. Topp M.S., Gökbuget N., Zugmaier G. et al. Phase II trial of the anti-CD19 bispecific T cell-engager blinatumomab shows hematologic and molecular remissions in patients with relapsed or refractory B-precursor acute lymphoblastic leukemia. J Clin Oncol 2014;32:4134–40.
65. Topp M.S., Gökbuget N., Stein A.S. et al. Safety and activity of blinatumomab for adult patients with relapsed or refractory Bprecursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. Lancet Oncol 2015;16:57–66.
Для цитирования:
Карачунский А.И., Румянцева Ю.В., фон Штакельберг А. Анти-CD19-моноклональные антитела при острой лимфобластной лейкемии у детей. Российский журнал детской гематологии и онкологии (РЖДГиО). 2016;3(4):60-72. https://doi.org/10.17650/2311-1267-2016-3-4-60-72
For citation:
Karachunskiy A.I., Rumyantseva Yu.V., fon Shtakelberg A. Anti-CD19 monoclonal antibodies in acute lymphoblastic leukemia in children. Russian Journal of Pediatric Hematology and Oncology. 2016;3(4):60-72. (In Russ.) https://doi.org/10.17650/2311-1267-2016-3-4-60-72
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