Engineering multivalent antibodies to target heregulin-induced HER3 signaling in breast cancer cells

mAbs

Volumn 6, Issue 2, 2014, Pages 340-353

  Kang, Jeffrey C ^a,b   Poovassery, Jayakumar S ^a,b   Bansal, Pankaj ^b   You, Sungyong ^a,b   Manjarres, Isabel M ^a,b   Ober, Raimund J ^a,b   Ward, E Sally ^b  

^a The University of Texas at Dallas   (United States)

^b UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

Author keywords

Antibody engineering; Bispecific antibody; HER2; HER3; Receptor internalization

Indexed keywords

BISPECIFIC ANTIBODY; EPIDERMAL GROWTH FACTOR RECEPTOR 2; EPIDERMAL GROWTH FACTOR RECEPTOR 3; LAPATINIB; NEU DIFFERENTIATION FACTOR; PERTUZUMAB; PHOSPHATIDYLINOSITOL 3 KINASE; SINGLE CHAIN FRAGMENT VARIABLE ANTIBODY; TRASTUZUMAB;

ANIMAL CELL; ANTIBODY ENGINEERING; ANTIPROLIFERATIVE ACTIVITY; ARTICLE; BREAST CANCER; CONTROLLED STUDY; DIMERIZATION; DRUG EFFICACY; FEMALE; HUMAN; HUMAN CELL; INTERNALIZATION; NONHUMAN; PROTEIN DEGRADATION; PROTEIN INTERACTION; SIGNAL TRANSDUCTION;

ANTIBODY ENGINEERING; BISPECIFIC ANTIBODY; HER2; HER3; RECEPTOR INTERNALIZATION;

ANIMALS; ANTIBODIES, MONOCLONAL, HUMANIZED; BREAST NEOPLASMS; CELL LINE, TUMOR; CHO CELLS; CRICETULUS; DRUG SYNERGISM; DRUG THERAPY, COMBINATION; EPITOPES; FEMALE; HUMANS; IMMUNOTHERAPY; MICE; MICE, INBRED BALB C; MICE, SCID; NEUREGULIN-1; PROTEIN BINDING; PROTEIN ENGINEERING; PROTEIN KINASE INHIBITORS; PROTEIN STABILITY; QUINAZOLINES; RECEPTOR, EPIDERMAL GROWTH FACTOR; RECEPTOR, ERBB-2; RECEPTOR, ERBB-3; RECOMBINANT FUSION PROTEINS; SIGNAL TRANSDUCTION;

EID: 84896524335     PISSN: 19420862     EISSN: 19420870     Source Type: Journal    
DOI: 10.4161/mabs.27658     Document Type: Article

References (62)

1. Lee-Hoeflich ST, Crocker L, Yao E, Pham T, Munroe X, Hoeflich KP, Sliwkowski MX, Stern HM. A central role for HER3 in HER2-amplified breast cancer: implications for targeted therapy. Cancer Res 2008; 68:5878-87; PMID:18632642; http://dx.doi.org/10.1158/0008-5472.CAN-08-0380
2. rd, Hynes NE. The ErbB2/ErbB3 heterodimer functions as an oncogenic unit: ErbB2 requires ErbB3 to drive breast tumor cell proliferation. Proc Natl Acad Sci U S A 2003; 100:8933-8; PMID:12853564; http://dx.doi.org/10.1073/pnas.1537685100
3. Schoeberl B, Faber AC, Li D, Liang MC, Crosby K, Onsum M, Burenkova O, Pace E, Walton Z, Nie L, et al. An ErbB3 antibody, MM-121, is active in cancers with ligand-dependent activation. Cancer Res 2010; 70:2485-94; PMID:20215504; http://dx.doi.org/10.1158/0008-5472.CAN-09-3145
4. Schoeberl B, Pace EA, Fitzgerald JB, Harms BD, Xu L, Nie L, Linggi B, Kalra A, Paragas V, Bukhalid R, et al. Therapeutically targeting ErbB3: a key node in ligand-induced activation of the ErbB receptor-PI3K axis. Sci Signal 2009; 2:ra31; PMID:19567914; http://dx.doi.org/10.1126/scisignal.2000352
5. Baselga J, Swain SM. Novel anticancer targets: revisiting ERBB2 and discovering ERBB3. Nat Rev Cancer 2009; 9:463-75; PMID:19536107; http://dx.doi.org/10.1038/nrc2656
6. Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol 2001; 2:127-37; PMID:11252954; http://dx.doi.org/10.1038/35052073
7. Tzahar E, Waterman H, Chen X, Levkowitz G, Karunagaran D, Lavi S, Ratzkin BJ, Yarden Y. A hierarchical network of interreceptor interactions determines signal transduction by Neu differentiation factor/neuregulin and epidermal growth factor. Mol Cell Biol 1996; 16:5276-87; PMID:8816440
8. Hellyer NJ, Kim MS, Koland JG. Heregulin-dependent activation of phosphoinositide 3-kinase and Akt via the ErbB2/ErbB3 co-receptor. J Biol Chem 2001; 276:42153-61; PMID:11546794; http://dx.doi.org/10.1074/jbc.M102079200
9. Campbell MR, Amin D, Moasser MM. HER3 comes of age: new insights into its functions and role in signaling, tumor biology, and cancer therapy. Clin Cancer Res 2010; 16:1373-83; PMID:20179223; http://dx.doi.org/10.1158/1078-0432.CCR- 09-1218
10. Murphy CG, Modi S. HER2 breast cancer therapies: a review. Biologics 2009; 3:289-301; PMID:19707416
11. Nahta R, Yu D, Hung MC, Hortobagyi GN, Esteva FJ. Mechanisms of disease: understanding resistance to HER2-targeted therapy in human breast cancer. Nat Clin Pract Oncol 2006; 3:269-80; PMID:16683005; http://dx.doi.org/10.1038/ ncponc0509
12. Hurvitz SA, Hu Y, O'Brien N, Finn RS. Current approaches and future directions in the treatment of HER2-positive breast cancer. Cancer Treat Rev 2013; 39:219-29; PMID:22658319; http://dx.doi.org/10.1016/j.ctrv.2012.04.008
13. Robinson MK, Hodge KM, Horak E, Sundberg AL, Russeva M, Shaller CC, von Mehren M, Shchaveleva I, Simmons HH, Marks JD, et al. Targeting ErbB2 and ErbB3 with a bispecific single-chain Fv enhances targeting selectivity and induces a therapeutic effect in vitro. Br J Cancer 2008; 99:1415-25; PMID:18841159; http://dx.doi.org/10.1038/sj.bjc.6604700
14. McDonagh CF, Huhalov A, Harms BD, Adams S, Paragas V, Oyama S, Zhang B, Luus L, Overland R, Nguyen S, et al. Antitumor activity of a novel bispecific antibody that targets the ErbB2/ErbB3 oncogenic unit and inhibits heregulin-induced activation of ErbB3. Mol Cancer Ther 2012; 11:582-93; PMID:22248472; http://dx.doi.org/10.1158/1535-7163.MCT-11-0820
15. Garrett JT, Sutton CR, Kuba MG, Cook RS, Arteaga CL. Dual blockade of HER2 in HER2-overexpressing tumor cells does not completely eliminate HER3 function. Clin Cancer Res 2013; 19:610-9; PMID:23224399; http://dx.doi.org/10. 1158/1078-0432.CCR-12-2024
16. Li Q, Ahmed S, Loeb JA. Development of an autocrine neuregulin signaling loop with malignant transformation of human breast epithelial cells. Cancer Res 2004; 64:7078-85; PMID:15466203; http://dx.doi.org/10.1158/0008-5472.CAN-04-1152
17. Montero JC, Rodríguez-Barrueco R, Ocaña A, Díaz-Rodríguez E, Esparís-Ogando A, Pandiella A. Neuregulins and cancer. Clin Cancer Res 2008; 14:3237-41; PMID:18519747; http://dx.doi.org/10.1158/1078-0432.CCR-07-5133
18. Dunn M, Sinha P, Campbell R, Blackburn E, Levinson N, Rampaul R, Bates T, Humphreys S, Gullick WJ. Co-expression of neuregulins 1, 2, 3 and 4 in human breast cancer. J Pathol 2004; 203:672-80; PMID:15141382; http://dx.doi.org/10. 1002/path.1561
19. Kaufman B, Trudeau M, Awada A, Blackwell K, Bachelot T, Salazar V, DeSilvio M, Westlund R, Zaks T, Spector N, et al. Lapatinib monotherapy in patients with HER2-overexpressing relapsed or refractory inflammatory breast cancer: final results and survival of the expanded HER2+ cohort in EGF103009, a phase II study. Lancet Oncol 2009; 10:581-8; PMID:19394894; http://dx.doi.org/ 10.1016/S1470-2045(09)70087-7
20. Gomez HL, Doval DC, Chavez MA, Ang PC, Aziz Z, Nag S, Ng C, Franco SX, Chow LW, Arbushites MC, et al. Efficacy and safety of lapatinib as first-line therapy for ErbB2-amplified locally advanced or metastatic breast cancer. J Clin Oncol 2008; 26:2999-3005; PMID:18458039; http://dx.doi.org/10.1200/JCO.2007.14. 0590
21. Burstein HJ, Sun Y, Dirix LY, Jiang Z, Paridaens R, Tan AR, Awada A, Ranade A, Jiao S, Schwartz G, et al. Neratinib, an irreversible ErbB receptor tyrosine kinase inhibitor, in patients with advanced ErbB2-positive breast cancer. J Clin Oncol 2010; 28:1301-7; PMID:20142587; http://dx.doi.org/10.1200/ JCO.2009.25.8707
22. Gradishar WJ. Emerging approaches for treating HER2-positive metastatic breast cancer beyond trastuzumab. Ann Oncol 2013; 24:2492-500; PMID:23827380; http://dx.doi.org/10.1093/annonc/mdt217
23. Baselga J, Albanell J, Ruiz A, Lluch A, Gascón P, Guillém V, González S, Sauleda S, Marimón I, Tabernero JM, et al. Phase II and tumor pharmacodynamic study of gefitinib in patients with advanced breast cancer. J Clin Oncol 2005; 23:5323-33; PMID:15939921; http://dx.doi.org/10.1200/ JCO.2005.08.326
24. Folkes AJ, Ahmadi K, Alderton WK, Alix S, Baker SJ, Box G, Chuckowree IS, Clarke PA, Depledge P, Eccles SA, et al. The identification of 2-(1H-indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morphol in-4-yl-thieno[3,2-d]pyrimidine (GDC-0941) as a potent, selective, orally bioavailable inhibitor of class I PI3 kinase for the treatment of cancer. J Med Chem 2008; 51:5522-32; PMID:18754654; http://dx.doi.org/10.1021/jm800295d
25. Brachmann SM, Hofmann I, Schnell C, Fritsch C, Wee S, Lane H, Wang S, Garcia-Echeverria C, Maira SM. Specific apoptosis induction by the dual PI3K/mTor inhibitor NVP-BEZ235 in HER2 amplified and PIK3CA mutant breast cancer cells. Proc Natl Acad Sci U S A 2009; 106:22299-304; PMID:20007781; http://dx.doi.org/10.1073/pnas.0905152106
26. Sergina NV, Rausch M, Wang D, Blair J, Hann B, Shokat KM, Moasser MM. Escape from HER-family tyrosine kinase inhibitor therapy by the kinase-inactive HER3. Nature 2007; 445:437-41; PMID:17206155; http://dx.doi.org/10.1038/ nature05474
27. Chakrabarty A, Sánchez V, Kuba MG, Rinehart C, Arteaga CL. Feedback upregulation of HER3 (ErbB3) expression and activity attenuates antitumor effect of PI3K inhibitors. Proc Natl Acad Sci U S A 2012; 109:2718-23; PMID:21368164; http://dx.doi.org/10.1073/pnas.1018001108
28. Scaltriti M, Verma C, Guzman M, Jimenez J, Parra JL, Pedersen K, Smith DJ, Landolfi S, Ramon y Cajal S, Arribas J, et al. Lapatinib, a HER2 tyrosine kinase inhibitor, induces stabilization and accumulation of HER2 and potentiates trastuzumab-dependent cell cytotoxicity. Oncogene 2009; 28:803-14; PMID:19060928; http://dx.doi.org/10.1038/onc.2008.432
29. Amin DN, Sergina N, Ahuja D, McMahon M, Blair JA, Wang D, Hann B, Koch KM, Shokat KM, Moasser MM. Resiliency and vulnerability in the HER2-HER3 tumorigenic driver. Sci Transl Med 2010; 2:ra7; PMID:20371474; http://dx.doi.org/10.1126/scitranslmed.3000389
30. Eichhorn PJ, Gili M, Scaltriti M, Serra V, Guzman M, Nijkamp W, Beijersbergen RL, Valero V, Seoane J, Bernards R, et al. Phosphatidylinositol 3-kinase hyperactivation results in lapatinib resistance that is reversed by the mTOR/phosphatidylinositol 3-kinase inhibitor NVP-BEZ235. Cancer Res 2008; 68:9221-30; PMID:19010894; http://dx.doi.org/10.1158/0008-5472.CAN-08-1740
31. Wilson TR, Fridlyand J, Yan Y, Penuel E, Burton L, Chan E, Peng J, Lin E, Wang Y, Sosman J, et al. Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors. Nature 2012; 487:505-9; PMID:22763448; http://dx.doi.org/10.1038/nature11249
32. rd, Zhao S, Liu L, Osada T, Cheng Q, Wulfkuhle JD, Gwin WR, Yang X, Gallagher RI, et al. An heregulin-EGFR-HER3 autocrine signaling axis can mediate acquired lapatinib resistance in HER2+ breast cancer models. Breast Cancer Res 2013; 15:R85; PMID:24044505; http://dx.doi.org/10.1186/bcr3480
33. Sato Y, Yashiro M, Takakura N. Heregulin induces resistance to lapatinib-mediated growth inhibition of HER2-amplified cancer cells. Cancer Sci 2013; 104:1618-25; PMID:24112719; http://dx.doi.org/10.1111/cas.12290
34. Engelman JA, Zejnullahu K, Mitsudomi T, Song Y, Hyland C, Park JO, Lindeman N, Gale CM, Zhao X, Christensen J, et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 2007; 316:1039-43; PMID:17463250; http://dx.doi.org/10.1126/science.1141478
35. Knowlden JM, Gee JM, Barrow D, Robertson JF, Ellis IO, Nicholson RI, Hutcheson IR. erbB3 recruitment of insulin receptor substrate 1 modulates insulin-like growth factor receptor signalling in oestrogen receptor-positive breast cancer cell lines. Breast Cancer Res 2011; 13:R93; PMID:21939528; http://dx.doi.org/10.1186/bcr3018
36. Sak MM, Breen K, Rønning SB, Pedersen NM, Bertelsen V, Stang E, Madshus IH. The oncoprotein ErbB3 is endocytosed in the absence of added ligand in a clathrin-dependent manner. Carcinogenesis 2012; 33:1031-9; PMID:22436610; http://dx.doi.org/10.1093/carcin/bgs128
37. Chan AC, Carter PJ. Therapeutic antibodies for autoimmunity and inflammation. Nat Rev Immunol 2010; 10:301-16; PMID:20414204; http://dx.doi.org/10.1038/nri2761
38. Sievers EL, Senter PD. Antibody-drug conjugates in cancer therapy. Annu Rev Med 2013; 64:15-29; PMID:23043493; http://dx.doi.org/10.1146/annurev-med- 050311-201823
39. Cho HS, Mason K, Ramyar KX, Stanley AM, Gabelli SB, Denney DW Jr., Leahy DJ. Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab. Nature 2003; 421:756-60; PMID:12610629; http://dx.doi.org/10. 1038/nature01392
40. Franklin MC, Carey KD, Vajdos FF, Leahy DJ, de Vos AM, Sliwkowski MX. Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex. Cancer Cell 2004; 5:317-28; PMID:15093539; http://dx.doi.org/10.1016/S1535- 6108(04)00083-2
41. Gymnopoulos M, Elsliger MA, Vogt PK. Rare cancer-specific mutations in PIK3CA show gain of function. Proc Natl Acad Sci U S A 2007; 104:5569-74; PMID:17376864; http://dx.doi.org/10.1073/pnas.0701005104
42. Weigelt B, Warne PH, Downward J. PIK3CA mutation, but not PTEN loss of function, determines the sensitivity of breast cancer cells to mTOR inhibitory drugs. Oncogene 2011; 30:3222-33; PMID:21358673; http://dx.doi.org/10.1038/onc. 2011.42
43. Junttila TT, Akita RW, Parsons K, Fields C, Lewis Phillips GD, Friedman LS, Sampath D, Sliwkowski MX. Ligand-independent HER2/HER3/PI3K complex is disrupted by trastuzumab and is effectively inhibited by the PI3K inhibitor GDC-0941. Cancer Cell 2009; 15:429-40; PMID:19411071; http://dx.doi.org/10.1016/ j.ccr.2009.03.020
44. Chandarlapaty S, Sawai A, Scaltriti M, Rodrik-Outmezguine V, Grbovic-Huezo O, Serra V, Majumder PK, Baselga J, Rosen N. AKT inhibition relieves feedback suppression of receptor tyrosine kinase expression and activity. Cancer Cell 2011; 19:58-71; PMID:21215704; http://dx.doi.org/10.1016/ j.ccr.2010.10.031
45. Serra V, Scaltriti M, Prudkin L, Eichhorn PJ, Ibrahim YH, Chandarlapaty S, Markman B, Rodriguez O, Guzman M, Rodriguez S, et al. PI3K inhibition results in enhanced HER signaling and acquired ERK dependency in HER2-overexpressing breast cancer. Oncogene 2011; 30:2547-57; PMID:21278786; http://dx.doi.org/10. 1038/onc.2010.626
46. Haslekås C, Breen K, Pedersen KW, Johannessen LE, Stang E, Madshus IH. The inhibitory effect of ErbB2 on epidermal growth factor-induced formation of clathrin-coated pits correlates with retention of epidermal growth factor receptor-ErbB2 oligomeric complexes at the plasma membrane. Mol Biol Cell 2005; 16:5832-42; PMID:16207817; http://dx.doi.org/10.1091/mbc.E05-05-0456
47. Sak MM, Szymanska M, Bertelsen V, Hasmann M, Madshus IH, Stang E. Pertuzumab counteracts the inhibitory effect of ErbB2 on degradation of ErbB3. Carcinogenesis 2013; 34:2031-8; PMID:23698633; http://dx.doi.org/10.1093/carcin/ bgt173
48. Le XF, McWatters A, Wiener J, Wu JY, Mills GB, Bast RC Jr. Anti-HER2 antibody and heregulin suppress growth of HER2-overexpressing human breast cancer cells through different mechanisms. Clin Cancer Res 2000; 6:260-70; PMID:10656457
49. Carter P, Presta L, Gorman CM, Ridgway JB, Henner D, Wong WL, Rowland AM, Kotts C, Carver ME, Shepard HM. Humanization of an anti-p185HER2 antibody for human cancer therapy. Proc Natl Acad Sci U S A 1992; 89:4285-9; PMID:1350088; http://dx.doi.org/10.1073/pnas.89.10.4285
50. Reichert JM, Dhimolea E. The future of antibodies as cancer drugs. Drug Discov Today 2012; 17:954-63; PMID:22561895; http://dx.doi.org/10.1016/j.drudis. 2012.04.006
51. Horak E, Heitner T, Robinson MK, Simmons HH, Garrison J, Russeva M, Furmanova P, Lou J, Zhou Y, Yuan QA, et al. Isolation of scFvs to in vitro produced extracellular domains of EGFR family members. Cancer Biother Radiopharm 2005; 20:603-13; PMID:16398612; http://dx.doi.org/10.1089/cbr.2005.20.603
52. Schier R, Marks JD, Wolf EJ, Apell G, Wong C, McCartney JE, Bookman MA, Huston JS, Houston LL, Weiner LM, et al. In vitro and in vivo characterization of a human anti-c-erbB-2 single-chain Fv isolated from a filamentous phage antibody library. Immunotechnology 1995; 1:73-81; PMID:9373335; http://dx.doi.org/10.1016/1380-2933(95)00007-0
53. Xu L, Kohli N, Rennard R, Jiao Y, Razlog M, Zhang K, Baum J, Johnson B, Tang J, Schoeberl B, et al. Rapid optimization and prototyping for therapeutic antibody-like molecules. MAbs 2013; 5:237-54; PMID:23392215; http://dx.doi.org/10.4161/mabs.23363
54. Fitzgerald JB, Johnson BW, Baum J, Adams S, Iadevaia S, Tang J, Rimkunas V, Xu L, Kohli N, Rennard R, et al. MM-141, an IGF-1R and ErbB3 directed bispecific antibody, overcomes network adaptations that limit activity of IGF-1R inhibitors. Mol Cancer Ther 2013; PMID:24282274; http://dx.doi.org/10.1158/ 1535-7163.MCT-13-0255
55. Jost C, Schilling J, Tamaskovic R, Schwill M, Honegger A, Plückthun A. Structural basis for eliciting a cytotoxic effect in HER2-overexpressing cancer cells via binding to the extracellular domain of HER2. Structure 2013; 21:1979-91; PMID:24095059; http://dx.doi.org/10.1016/j.str.2013.08.020
56. Foote J, Winter G. Antibody framework residues affecting the conformation of the hypervariable loops. J Mol Biol 1992; 224:487-99; PMID:1560463; http://dx.doi.org/10.1016/0022-2836(92)91010-M
57. Coloma MJ, Morrison SL. Design and production of novel tetravalent bispecific antibodies. Nat Biotechnol 1997; 15:159-63; PMID:9035142; http://dx.doi.org/10.1038/nbt0297-159
58. Zhou J, Mateos F, Ober RJ, Ward ES. Conferring the binding properties of the mouse MHC class I-related receptor, FcRn, onto the human ortholog by sequential rounds of site-directed mutagenesis. J Mol Biol 2005; 345:1071-81; PMID:15644205; http://dx.doi.org/10.1016/j.jmb.2004.11.014
59. Vaccaro C, Zhou J, Ober RJ, Ward ES. Engineering the Fc region of immunoglobulin G to modulate in vivo antibody levels. Nat Biotechnol 2005; 23:1283-8; PMID:16186811; http://dx.doi.org/10.1038/nbt1143
60. Vaccaro C, Bawdon R, Wanjie S, Ober RJ, Ward ES. Divergent activities of an engineered antibody in murine and human systems have implications for therapeutic antibodies. Proc Natl Acad Sci U S A 2006; 103:18709-14; PMID:17116867; http://dx.doi.org/10.1073/pnas.0606304103
61. Ober RJ, Martinez C, Vaccaro C, Zhou J, Ward ES. Visualizing the site and dynamics of IgG salvage by the MHC class I-related receptor, FcRn. J Immunol 2004; 172:2021-9; PMID:14764666
62. Gan Z, Ram S, Vaccaro C, Ober RJ, Ward ES. Analyses of the recycling receptor, FcRn, in live cells reveal novel pathways for lysosomal delivery. Traffic 2009; 10:600-14; PMID:19192244; http://dx.doi.org/10.1111/j.1600-0854. 2009.00887.x