Fc-engineered anti-CD40 antibody enhances multiple effector functions and exhibits potent in vitro and in vivo antitumor activity against hematologic malignancies

Blood

Volumn 116, Issue 16, 2010, Pages 3004-3012

  Horton, Holly M ^a   Bernett, Matthew J ^a   Peipp, Matthias ^b   Pong, Erik ^a   Karki, Sher ^a   Chu, Seung Y ^a   Richards, John O ^a,c   Chen, Hsing ^a   Repp, Roland ^b   Desjarlais, John R ^a   Zhukovsky, Eugene A ^a,d  

^a Xencor Inc   (United States)

^b UNIVERSITY OF KIEL   (Germany)

^c AURORA HEALTH CARE   (United States)

^d BOEHRINGER INGELHEIM PHARMACEUTICALS INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CD20 ANTIGEN; CD40 ANTIGEN; CD40 LIGAND MONOCLONAL ANTIBODY; FC RECEPTOR; IMMUNOGLOBULIN G1 ANTIBODY; RITUXIMAB;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIBODY DEPENDENT CELLULAR CYTOTOXICITY; ANTINEOPLASTIC ACTIVITY; ARTICLE; B CELL LYMPHOMA; BINDING AFFINITY; CELL PROLIFERATION; CONTROLLED STUDY; CYTOTOXICITY; DOSE RESPONSE; DRUG SYNTHESIS; FEMALE; HEMATOLOGIC DISEASE; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; LEUKEMIA; MOUSE; MULTIPLE MYELOMA; NONHUMAN; PHAGOCYTOSIS; PRIORITY JOURNAL; PROTEIN BINDING; SURVIVAL RATE; TUMOR GROWTH;

EID: 77958167235     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2010-01-265280     Document Type: Article

References (51)

1. Robak T. Monoclonal antibodies in the treatment of chronic lymphoid leukemias. Leuk Lymphoma. 2004;45(2):205-219. (Pubitemid 38181421)
2. Bello C, Sotomayor EM. Monoclonal antibodies for B-cell lymphomas: rituximab and beyond. Hematology Am Soc Hematol Educ Program. 2007;233-242.
3. Castillo J, Milani C, Mendez-Allwood D. Ofatumumab, a second-generation anti-CD20 monoclonal antibody, for the treatment of lymphoproliferative and autoimmune disorders. Expert Opin Investig Drugs. 2009;18(4):491-500.
4. Chinn P, Braslawsky G, White C, Hanna N. Antibody therapy of non-Hodgkin's B-cell lymphoma. Cancer Immunol Immunother. 2003;52(5):257-280. (Pubitemid 36581906)
5. Vose JM. Bexxar: novel radioimmunotherapy for the treatment of low-grade and transformed low-grade non-Hodgkin's lymphoma. Oncologist. 2004;9(2):160-172.
6. Fanale MA, Younes A. Monoclonal antibodies in the treatment of non-Hodgkin's lymphoma. Drugs. 2007;67(3):333-350. (Pubitemid 46425549)
7. Kennedy GA, Tey SK, Cobcroft R, et al. Incidence and nature of CD20-negative relapses following rituximab therapy in aggressive B-cell non-Hodgkin's lymphoma: a retrospective review. Br J Haematol. 2002;119(2):412-416.
8. Banchereau J, Bazan F, Blanchard D, et al. The CD40 antigen and its ligand. Annu Rev Immunol. 1994;12:881-922.
9. van Kooten C, Banchereau J. Functions of CD40 on B cells, dendritic cells and other cells. Curr Opin Immunol. 1997;9(3):330-337. (Pubitemid 27303501)
10. Grewal IS, Flavell RA. CD40 and CD154 in cellmediated immunity. Annu Rev Immunol. 1998;16:111-135.
11. O'Grady JT, Stewart S, Lowrey J, Howie SE, Krajewski AS. CD40 expression in Hodgkin's disease. Am J Pathol. 1994;144(1):21-26.
12. Wang D, Freeman GJ, Levine H, Ritz J, Robertson MJ. Role of the CD40 and CD95 (APO-1/Fas) antigens in the apoptosis of human B-cell malignancies. Br J Haematol. 1997;97(2):409-417.
13. Pellat-Deceunynck C, Bataille R, Robillard N, et al. Expression of CD28 and CD40 in human myeloma cells: a comparative study with normal plasma cells. Blood. 1994;84(8):2597-2603. (Pubitemid 24317392)
14. Ottaiano A, Pisano C, De Chiara A, et al. CD40 activation as potential tool in malignant neoplasms. Tumori. 2002;88(5):361-366.
15. French RR, Chan HT, Tutt AL, Glennie MJ. CD40 antibody evokes a cytotoxic T-cell response that eradicates lymphoma and bypasses T-cell help. Nat Med. 1999;5(5):548-553.
16. van Mierlo GJ, den Boer AT, Medema JP, et al. CD40 stimulation leads to effective therapy of CD40(-) tumors through induction of strong systemic cytotoxic T lymphocyte immunity. Proc Natl Acad Sci U S A. 2002;99(8):5561-5566.
17. Eliopoulos AG, Young LS. The role of the CD40 pathway in the pathogenesis and treatment of cancer. Curr Opin Pharmacol. 2004;4(4):360-367.
18. Gladue RP, Cole SH, Donovan C, et al. In vivo efficacy of the CD40 agonist antibody CP-870,893 against a broad range of tumor types: impact of tumor CD40 expression, dendritic cells, and chemotherapy [abstract]. J Clin Oncol. 2006;24(103s). Abstract 2514.
19. Funakoshi S, Longo DL, Beckwith M, et al. Inhibition of human B-cell lymphoma growth by CD40 stimulation. Blood. 1994;83(10):2787-2794.
20. Law CL, Gordon KA, Collier J, et al. Preclinical antilymphoma activity of a humanized anti-CD40 monoclonal antibody, SGN-40. Cancer Res. 2005;65(18):8331-8338.
21. Luqman M, Klabunde S, Lin K, et al. The antileukemia activity of a human anti-CD40 antagonist antibody, HCD122, on human chronic lymphocytic leukemia cells. Blood. 2008;112(3):711-720.
22. Szocinski JL, Khaled AR, Hixon J, et al. Activation-induced cell death of aggressive histology lymphomas by CD40 stimulation: induction of bax. Blood. 2002;100(1):217-223.
23. Tai YT, Li X, Tong X, et al. Human anti-CD40 antagonist antibody triggers significant antitumor activity against human multiple myeloma. Cancer Res. 2005;65(13):5898-5906.
24. Kelley SK, Gelzleichter T, Xie D, et al. Preclinical pharmacokinetics, pharmacodynamics, and activity of a humanized anti-CD40 antibody (SGN-40) in rodents and non-human primates. Br J Pharmacol. 2006;148(8):1116-1123.
25. Tai YT, Catley LP, Mitsiades CS, et al. Mechanisms by which SGN-40, a humanized anti-CD40 antibody, induces cytotoxicity in human multiple myeloma cells: clinical implications. Cancer Res. 2004;64(8):2846-2852.
26. Advani R, De Vos S, Ansell SM, et al. A phase 2 clinical trial of SGN-40 monotherapy in relapsed diffuse large B-cell lymphoma [abstract]. Blood. 2008;112(11). Abstract 1000.
27. Hussein MA, Berenson JR, Niesvizky R, et al. Results of a phase I trial of SGN-40 (anti-huCD40 mAb) in patients with relapsed multiple myeloma [abstract]. Blood. 2006;108(11). Abstract 3576.
28. Bensinger W, Jagannath S, Becker PS, et al. A phase I dose escalation study of a fully human, antagonist anti-CD40 antibody, HCD122 (formerly CHIR-12.12) in patients with relapse and refractory multiple myeloma [abstract]. Blood. 2006;108. Abstract 3575.
29. Vonderheide RH, Flaherty KT, Khalil M, et al. Clinical activity and immune modulation in cancer patients treated with CP-870,893, a novel CD40 agonist monoclonal antibody. J Clin Oncol. 2007;25(7):876-883.
30. Desjarlais JR, Lazar GA, Zhukovsky EA, Chu SY. Optimizing engagement of the immune system by anti-tumor antibodies: an engineer's perspective. Drug Discov Today. 2007;12(21):898-910.
31. Bowles JA, Wang SY, Link BK, 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(8):2648-2654.
32. Lazar GA, Dang W, Karki S, et al. Engineered antibody Fc variants with enhanced effector function. Proc Natl Acad Sci U S A. 2006;103(11):4005-4010.
33. Richards JO, Karki S, Lazar GA, Chen H, Dang W, Desjarlais JR. Optimization of antibody binding to FcgammaRIIa enhances macrophage phagocytosis of tumor cells. Mol Cancer Ther. 2008;7(8):2517-2527.
34. Shields RL, Namenuk AK, Hong K, et al. High resolution mapping of the binding site on human IgG1 for FcgammaRI, FcgammaRII, FcgammaRIII, and FcRn and design of IgG1 variants with improved binding to the FcγR. J Biol Chem. 2001;276(9):6591-6604.
35. Stavenhagen JB, Gorlatov S, Tuaillon N, et al. Fc optimization of therapeutic antibodies enhances their ability to kill tumor cells in vitro and controls tumor expansion in vivo via low-affinity activating Fcgamma receptors. Cancer Res. 2007;67(18):8882-8890.
36. Horton HM, Bernett MJ, Pong E, et al. Potent in vitro and in vivo activity of an Fc-engineered anti-CD19 monoclonal antibody against lymphoma and leukemia. Cancer Res. 2008;68(19):8049-8057.
37. Blum KA, Smith M, Fung H, et al. Phase I study of an anti-CD30 Fc engineered humanized monoclonal antibody in Hodgkin lymphoma (HL) or anaplastic large cell lymphoma (ALCL) patients: safety, pharmacokinetics (PK), immunogenicity, and efficacy [abstract]. J Clin Oncol. 2009;27(15s). Abstract 8531.
38. Koho H, Paulie S, Ben-Aissa H, et al. Monoclonal antibodies to antigens associated with transitional cell carcinoma of the human urinary bladder: I. Determination of the selectivity of six antibodies by cell ELISA and immunofluorescence. Cancer Immunol Immunother. 1984;17(3):165-172. (Pubitemid 14073622)
39. Paulie S, Koho H, Ben-Aissa H, Hansson Y, Lundblad ML, Perlmann P. Monoclonal antibodies to antigens associated with transitional cell carcinoma of the human urinary bladder: II. Identification of the cellular target structures by immunoprecipitation and SDS-PAGE analysis. Cancer Immunol Immunother. 1984;17(3):173-179. (Pubitemid 14073623)
40. Lazar GA, Desjarlais JR, Jacinto J, Karki S, Hammond PW. A molecular immunology approach to antibody humanization and functional optimization. Mol Immunol. 2007;44(8):1986-1998. (Pubitemid 44827249)
41. Moore GL, Chen H, Karki S, Lazar GA. Engineered Fc variant antibodies with enhanced ability to recruit complement and mediate effector functions. MAbs. 2010;2(2):181-189.
42. Oflazoglu E, Stone IJ, Brown L, et al. Macrophages and Fc-receptor interactions contribute to the antitumour activities of the anti-CD40 antibody SGN-40. Br J Cancer. 2009;100(1):113-117.
43. McEarchern JA, Oflazoglu E, Francisco L, et al. Engineered anti-CD70 antibody with multiple effector functions exhibits in vitro and in vivo antitumor activities. Blood. 2007;109(3):1185-1192.
44. Tedder TF, Baras A, Xiu Y. Fcgamma receptor-dependent effector mechanisms regulate CD19 and CD20 antibody immunotherapies for B lymphocyte malignancies and autoimmunity. Springer Semin Immunopathol. 2006;28(4):351-364.
45. Turner JG, Rakhmilevich AL, Burdelya L, et al. Anti-CD40 antibody induces antitumor and anti-metastatic effects: the role of NK cells. J Immunol. 2001;166(1):89-94. (Pubitemid 32038420)
46. Nimmerjahn F, Ravetch JV. Fcgamma receptors: old friends and new family members. Immunity. 2006;24(1):19-28.
47. Cartron G, Dacheux L, Salles G, et al. Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcgammaRIIIa gene. Blood. 2002;99(3):754-758.
48. Treon SP, Hansen M, Branagan AR, et al. Polymorphisms in FcγRIIIA (CD16) receptor expression are associated with clinical response to rituximab in Waldenstrom's macroglobulinemia. J Clin Oncol. 2005;23(3):474-481.
49. Bowles JA, Weiner GJ. CD16 polymorphisms and NK activation induced by monoclonal antibody-coated target cells. J Immunol Methods. 2005;304(1):88-99.
50. Zalevsky J, Leung IW, Karki S, et al. The impact of Fc engineering on an anti-CD19 antibody: increased Fcgamma receptor affinity enhances Bcell clearing in nonhuman primates. Blood. 2009;113(16):3735-3743.
51. Meropol NJ, Barresi GM, Fehniger TA, Hitt J, Franklin M, Caligiuri MA. Evaluation of natural killer cell expansion and activation in vivo with daily subcutaneous low-dose interleukin-2 plus periodic intermediate-dose pulsing. Cancer Immunol Immunother. 1998;46(6):318-326. (Pubitemid 28410578)