Blinatumomab: A CD19/CD3 bispecific T cell engager (BiTE) with unique anti-tumor efficacy

Leukemia and Lymphoma

Volumn 57, Issue 5, 2016, Pages 1021-1032

  Goebeler, Maria Elisabeth ^a   Bargou, Ralf ^a  

^a UNIVERSITY HOSPITAL WÜRZBURG   (Germany)

Author keywords

B precursor ALL; BiTEVR; blinatumomab; immunotherapy; NHL

Indexed keywords

B LYMPHOCYTE RECEPTOR; BISPECIFIC ANTIBODY; BISPECIFIC T CELL ENGAGER; BLINATUMOMAB; CD19 ANTIGEN; CD3 ANTIGEN; FLUDARABINE; RITUXIMAB; UNCLASSIFIED DRUG; ANTINEOPLASTIC AGENT;

ACUTE LYMPHOBLASTIC LEUKEMIA; ANEMIA; ANTINEOPLASTIC ACTIVITY; APHASIA; ARTICLE; ATAXIA; BRAIN DISEASE; CHILL; CONFUSION; CONSOLIDATION CHEMOTHERAPY; CONSTIPATION; CONTINUOUS INFUSION; COST EFFECTIVENESS ANALYSIS; CYTOKINE RELEASE SYNDROME; DEVICE INFECTION; DISORIENTATION; DRUG DOSE ESCALATION; DRUG ERUPTION; DRUG FEVER; DRUG HALF LIFE; DRUG INDUCED HEADACHE; DRUG MECHANISM; DRUG WITHDRAWAL; EVENT FREE SURVIVAL; EXPERIMENTAL THERAPY; FATIGUE; FEBRILE NEUTROPENIA; FLU LIKE SYNDROME; FOLLICULAR LYMPHOMA; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HUMAN; HYPOKALEMIA; LARGE CELL LYMPHOMA; LEUKOPENIA; LYMPHOCYTOPENIA; MANTLE CELL LYMPHOMA; MAXIMUM TOLERATED DOSE; MONOTHERAPY; NAUSEA; NEUTROPENIA; NONHODGKIN LYMPHOMA; OVERALL SURVIVAL; PERIPHERAL EDEMA; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PNEUMONIA; PRIORITY JOURNAL; QUALITY OF LIFE; SEIZURE; SEPSIS; STAPHYLOCOCCAL BACTEREMIA; T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION; TREMOR; ANIMAL; CLINICAL TRIAL (TOPIC); COST BENEFIT ANALYSIS; DRUG EFFECTS; DRUG RESISTANCE; ECONOMICS; IMMUNOLOGY; LYMPHOMA, NON-HODGKIN; METABOLISM; MOLECULARLY TARGETED THERAPY; NEOPLASMS; PATHOLOGY; PRECLINICAL STUDY; PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA; RECURRENT DISEASE; TREATMENT OUTCOME;

ANIMALS; ANTIBODIES, BISPECIFIC; ANTIGENS, CD19; ANTIGENS, CD3; ANTINEOPLASTIC AGENTS; CLINICAL TRIALS AS TOPIC; COST-BENEFIT ANALYSIS; DRUG EVALUATION, PRECLINICAL; DRUG RESISTANCE, NEOPLASM; HUMANS; LYMPHOMA, NON-HODGKIN; MOLECULAR TARGETED THERAPY; NEOPLASMS; PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA; RECURRENCE; T-LYMPHOCYTES; TREATMENT OUTCOME;

EID: 84962466993     PISSN: 10428194     EISSN: 10292403     Source Type: Journal    
DOI: 10.3109/10428194.2016.1161185     Document Type: Article

References (65)

1. McLaughlin P, Grillo-Lopez AJ, Link BK., et al. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol. 1998; 16: 2825-2833.
2. Cheson BD, Leonard JP. Monoclonal antibody therapy for B-cell non-Hodgkin's lymphoma. N Engl J Med. 2008; 359: 613-626.
3. Van Cutsem E, Peeters M, Siena S., et al. Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol. 2007; 25: 1658-1664.
4. Hurwitz HI, Tebbutt NC, Kabbinavar F., et al. Efficacy and safety of bevacizumab in metastatic colorectal cancer: pooled analysis from seven randomized controlled trials. Oncologist. 2013; 18: 1004-1012.
5. Ducreux M, Adenis A, Pignon JP., et al. Efficacy and safety of bevacizumab-based combination regimens in patients with previously untreated metastatic colorectal cancer: final results from a randomised phase II study of bevacizumab plus 5-fluorouracil, leucovorin plus irinotecan versus bevacizumab plus capecitabine plus irinotecan (FNCLCC ACCORD 13/0503 study). Eur J Cancer. 2013; 49: 1236-1245.
6. Slamon DJ, Leyland-Jones B, Shak S., et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001; 344: 783-792.
7. Younes A, Bartlett NL, Leonard JP., et al. Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas. N Engl J Med. 2010; 363: 1812-1821.
8. Ansell SM, Horwitz SM, Engert A., et al. Phase I/II study of an anti-CD30 monoclonal antibody (MDX-060) in Hodgkin's lymphoma and anaplastic large-cell lymphoma. J Clin Oncol. 2007; 25: 2764-2769.
9. Chames P, Van Regenmortel M, Weiss E., et al. Therapeutic antibodies: successes, limitations and hopes for the future. Br J Pharmacol. 2009; 157: 220-233.
10. Brody J, Kohrt H, Marabelle A., et al. Active and passive immunotherapy for lymphoma: proving principles and improving results. J Clin Oncol. 2011; 29: 1864-1875.
11. Pardoll DM. Immunology beats cancer: a blueprint for successful translation. Nat Immunol. 2012; 13: 1129-1132.
12. Nelson MH, Paulos CM. Novel immunotherapies for hematologic malignancies. Immunol Rev. 2015; 263: 90-105.
13. Porter DL, Levine BL, Kalos M., et al. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med. 2011; 365: 725-733.
14. Lee DW, Kochenderfer JN, Stetler-Stevenson M., et al. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet. 2015; 385: 517-528.
15. Johnsen AK, Templeton DJ, Sy M., et al. Deficiency of transporter for antigen presentation (TAP) in tumor cells allows evasion of immune surveillance and increases tumorigenesis. J Immunol. 1999; 163: 4224-4231.
16. Ritz U, Momburg F, Pilch H., et al. Deficient expression of components of the MHC class I antigen processing machinery in human cervical carcinoma. Int J Oncol. 2001; 19: 1211-1220.
17. Bubenik J. Tumour MHC class I downregulation and immunotherapy (Review). Oncol Rep. 2003; 10: 2005-2008.
18. Abrams SI. Positive and negative consequences of Fas/Fas ligand interactions in the antitumor response. Front Biosci. 2005; 10: 809-821.
19. Iwai Y, Terawaki S, Honjo T. PD-1 blockade inhibits hematogenous spread of poorly immunogenic tumor cells by enhanced recruitment of effector T cells. Int Immunol. 2005; 17: 133-144.
20. Mittal D, Gubin MM, Schreiber RD., et al. New insights into cancer immunoediting and its three component phases-elimination, equilibrium and escape. Curr Opin Immunol. 2014; 27: 16-25.
21. Frankel SR, Baeuerle PA. Targeting T cells to tumor cells using bispecific antibodies. Curr Opin Chem Biol. 2013; 17: 385-392.
22. Mack M, Riethmuller G, Kufer P. A small bispecific antibody construct expressed as a functional single-chain molecule with high tumor cell cytotoxicity. Proc Natl Acad Sci USA. 1995; 92: 7021-7025.
23. Loffler A, Kufer P, Lutterbuse R., et al. A recombinant bispecific single-chain antibody, CD19 x CD3, induces rapid and high lymphoma-directed cytotoxicity by unstimulated T lymphocytes. Blood. 2000; 95: 2098-2103.
24. Dreier T, Lorenczewski G, Brandl C., et al. Extremely potent, rapid and costimulation-independent cytotoxic T-cell response against lymphoma cells catalyzed by a single-chain bispecific antibody. Int J Cancer. 2002; 100: 690-697.
25. Nagorsen D, Bargou R, Ruttinger D., et al. Immunotherapy of lymphoma and leukemia with T-cell engaging BiTE antibody blinatumomab. Leuk Lymphoma. 2009; 50: 886-891.
26. Nagorsen D, Baeuerle PA. Immunomodulatory therapy of cancer with T cell-engaging BiTE antibody blinatumomab. Exp Cell Res. 2011; 317: 1255-1260.
27. Kufer P, Zettl F, Borschert K., et al. Minimal costimulatory requirements for T cell priming and TH1 differentiation: activation of naive human T lymphocytes by tumor cells armed with bifunctional antibody constructs. Cancer Immun. 2001; 1: 10.
28. Wolf E, Hofmeister R, Kufer P., et al. BiTEs: bispecific antibody constructs with unique anti-tumor activity. Drug Discov Today. 2005; 10: 1237-1244.
29. Dreier T, Baeuerle PA, Fichtner I., et al. T cell costimulus-independent and very efficacious inhibition of tumor growth in mice bearing subcutaneous or leukemic human B cell lymphoma xenografts by a CD19-/CD3-bispecific single-chain antibody construct. J Immunol. 2003; 170: 4397-4402.
30. 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 single-chain antibody construct. Cancer Immunol Immunother. 2007; 56: 1551-1563.
31. Nagorsen D, Kufer P, Baeuerle PA., et al. Blinatumomab: a historical perspective. Pharmacol Ther. 2012; 136: 334-342.
32. Baeuerle PA, Reinhardt C. Bispecific T-cell engaging antibodies for cancer therapy. Cancer Res. 2009; 69: 4941-4944.
33. 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: 763-771.
34. Gruen M, Bommert K, Bargou RC. T-cell-mediated lysis of B cells induced by a CD19xCD3 bispecific single-chain antibody is perforin dependent and death receptor independent. Cancer Immunol Immunother. 2004; 53: 625-632.
35. Haas C, Krinner E, Brischwein K., et al. Mode of cytotoxic action of T cell-engaging BiTE antibody MT110. Immunobiology. 2009; 214: 441-453.
36. Brischwein K, Schlereth B, Guller B., et al. MT110: a novel bispecific single-chain antibody construct with high efficacy in eradicating established tumors. Mol Immunol. 2006; 43: 1129-1143.
37. 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.
38. Carter RH, Barrington RA. Signaling by the CD19/CD21 complex on B cells. Curr Dir Autoimmun. 2004; 7: 4-32.
39. Carter RH, Myers R. Germinal center structure and function: lessons from CD19. Semin Immunol. 2008; 20: 43-48.
40. Tedder TF. CD19: a promising B cell target for rheumatoid arthritis. Nat Rev Rheumatol. 2009; 5: 572-577.
41. Raponi S, De Propris MS, Intoppa S., et al. Flow cytometric study of potential target antigens (CD19, CD20, CD22, CD33) for antibody-based immunotherapy in acute lymphoblastic leukemia: analysis of 552 cases. Leuk Lymphoma. 2011; 52: 1098-1107.
42. Teachey DT, Rheingold SR, Maude SL., et al. Cytokine release syndrome after blinatumomab treatment related to abnormal macrophage activation and ameliorated with cytokine-directed therapy. Blood. 2013; 121: 5154-5157.
43. Wang K, Wei G, Liu D. CD19: a biomarker for B cell development, lymphoma diagnosis and therapy. Exp Hematol Oncol. 2012; 1: 36.
44. Tedder TF, Inaoki M, Sato S. The CD19-CD21 complex regulates signal transduction thresholds governing humoral immunity and autoimmunity. Immunity. 1997; 6: 107-118.
45. Khwaja A. PI3K as a target for therapy in haematological malignancies. Curr Top Microbiol Immunol. 2010; 347: 169-188.
46. Weiland J, Elder A, Forster V., et al. CD19: A multifunctional immunological target molecule and its implications for Blineage acute lymphoblastic leukemia. Pediatr Blood Cancer. 2015; 62: 1144-1148.
47. 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: 974-977.
48. Goebeler ME, Knop S, Viardot A., et al. Bispecific T-cell engager (BiTE) antibody blinatumomab for the treatment of patients with relapsed/refractory non-Hodgkin lymphoma: final results from a phase 1 study. J Clin Oncol. 2016; pii: JCO591586 [Epub ahead of print].
49. Viardot A, Goebeler ME, Hess G., et al. Phase 2 study of bispecific T-cell engager (BiTE®) antibody blinatumomab in relapsed/refractory diffuse large B cell lymphoma. Blood 2016; pii: blood-2015-06-651380 [Epub ahead of print].
50. Raff T, Gokbuget N, Luschen S., et al. Molecular relapse in adult standard-risk ALL patients detected by prospective MRD monitoring during and after maintenance treatment: data from the GMALL 06/99 and 07/03 trials. Blood. 2007; 109: 910-915.
51. Topp MS, Kufer P, Gokbuget N., et al. Targeted therapy with the T-cell-engaging antibody blinatumomab of chemotherapy-refractory minimal residual disease in B-lineage acute lymphoblastic leukemia patients results in high response rate and prolonged leukemia-free survival. J Clin Oncol. 2011; 29: 2493-2498.
52. Topp MS, Gokbuget N, Zugmaier G., et al. Long-term follow-up of hematologic relapse-free survival in a phase 2 study of blinatumomab in patients with MRD in B-lineage ALL. Blood. 2012; 120: 5185-5187.
53. Goekbuget N, Dombret H, Bonifacio M., et al. BLAST: a confirmatory, single-Arm, phase 2 study of blinatumomab, a bispecific T-cell engager (BiTE®) antibody construct, in patients with minimal residual disease B-precursor acute lymphoblastic leukemia (ALL). Blood. 2014; 124: 379.
54. Topp MS, Gokbuget 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: 4134-4140.
55. Topp MS, Gokbuget N, Stein AS., et al. Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-Arm, phase 2 study. Lancet Oncol. 2015; 16: 57-66.
56. Handgretinger R, Zugmaier G, Henze G., et al. Complete remission after blinatumomab-induced donor T-cell activation in three pediatric patients with post-transplant relapsed acute lymphoblastic leukemia. Leukemia. 2011; 25: 181-184.
57. Schlegel P, Lang P, Zugmaier G., et al. Pediatric posttransplant relapsed/refractory B-precursor acute lymphoblastic leukemia shows durable remission by therapy with the T-cell engaging bispecific antibody blinatumomab. Haematologica. 2014; 99: 1212-1219.
58. von Stackelberg A, Locatelli F, Zugmaier G., et al. Phase 1/2 study in pediatric patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL) receiving blinatumomab treatment. Blood. 2014; 124: 61.
59. Gore L, Locatelli F, Zugmaier G., et al. Initial results from a phase 2 study of blinatumomab in pediatric patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia. Blood. 2014; 124: 3703.
60. Vedi A, Ziegler DS. Antibody therapy for pediatric leukemia. Front Oncol. 2014; 4: 82.
61. Barrett DM, Teachey DT, Grupp SA. Toxicity management for patients receiving novel T-cell engaging therapies. Curr Opin Pediatr. 2014; 26: 43-49.
62. Maude SL, Frey N, Shaw PA., et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014; 371: 1507-1517.
63. 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: 6226-6233.
64. Duell J, Dittrich M, Bedke T., et al. Crucial role of regulatory T cells in predicting the outcome of the T cell engaging antibody blinatumomab in relapsed and refractory B precursor ALL patients. Blood. 2014; 124: 2291.
65. Zimmerman Z, Maniar T, Nagorsen D. Unleashing the clinical power of T cells: CD19/CD3 bi-specific T cell engager (BiTE(R)) antibody construct blinatumomab as a potential therapy. Int Immunol. 2015; 27: 31-37.