Chemoenzymatic Conjugation of Toxic Payloads to the Globally Conserved N-Glycan of Native mAbs Provides Homogeneous and Highly Efficacious Antibody-Drug Conjugates

Bioconjugate Chemistry

Volumn 26, Issue 11, 2015, Pages 2233-2242

  Van Geel, Remon ^a   Wijdeven, Marloes A ^a   Heesbeen, Ryan ^a   Verkade, Jorge M M ^a   Wasiel, Anna A ^a   Van Berkel, Sander S ^a   Van Delft, Floris L ^a  

^a SynAffix BV   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACIDS; COPPER; FLUORINE COMPOUNDS; MONOCLONAL ANTIBODIES; POLYSACCHARIDES; SURFACE PLASMON RESONANCE;

ANTIBODY-DRUG CONJUGATES; CLICK CHEMISTRY; COPPER-FREE CLICKS; ENZYMATIC REMODELING; GLYCOSYLATIONS; IN-VITRO; MAYTANSINE; N-GLYCAN; TRASTUZUMAB; TWO-STAGE PROCESS;

GLYCOSYLATION;

2 AZIDO 2 DEOXY ALPHA DEXTRO GALACTOSE; 3,4,6 TRI O ACETYL 2 AZIDO 2 DEOXY ALPHA DEXTRO GALACTOSE 1 PHOSPHATE; 3,4,6 TRI O ACETYL ALPHA DEXTRO GALACTOSAMINE 1 PHOSPHATE; 3,4,6 TRI O ACETYL N (2' AZIDO 2',2' DIFLUOROACETYL) ALPHA DEXTRO GALACTOSAMINE 1 PHOSPHATE; ASPARAGINE; CYTOTOXIC AGENT; GLYCAN; IMMUNOGLOBULIN G; MAYTANSINE; MONOCLONAL ANTIBODY; TRASTUZUMAB; TRASTUZUMAB EMTANSINE; UNCLASSIFIED DRUG; URIDINE DIPHOSPHATE 2 (2' AZIDO 2',2' DIFLUOROACETYL) ALPHA DEXTRO GALACTOSAMINE; URIDINE DIPHOSPHATE 2 (4' AZIDO 3',5' DIFLUOROBENZOYL) ALPHA DEXTRO GALACTOSAMINE; URIDINE DIPHOSPHATE 3,4,6 TRI DEXTRO O ACETYL 2 AZIDO 2 DEOXY ALPHA DEXTRO GALACTOSE; URIDINE DIPHOSPHATE 3,4,6 TRI O ACETYL N (2' AZIDO 2',2' DIFLUOROACETYL) ALPHA DEXTRO GALACTOSAMINE; URIDINE DIPHOSPHATE ALPHA DEXTRO GALACTOSAMINE; ANTIBODY CONJUGATE; AZIDE; POLYSACCHARIDE;

ANIMAL EXPERIMENT; ARTICLE; CLICK CHEMISTRY; CONTROLLED STUDY; DRUG CONJUGATION; DRUG EFFICACY; GLYCOSYLATION; IN VITRO STUDY; IN VIVO STUDY; MOUSE; NONHUMAN; SINGLE DRUG DOSE; TUMOR REGRESSION; ANALOGS AND DERIVATIVES; CARBOHYDRATE ANALYSIS; CHEMICAL STRUCTURE; CHEMISTRY; HUMAN; MOLECULAR GENETICS; PROTEIN STABILITY;

ANTIBODIES, MONOCLONAL; ANTIBODIES, MONOCLONAL, HUMANIZED; AZIDES; CARBOHYDRATE SEQUENCE; CLICK CHEMISTRY; GLYCOSYLATION; HUMANS; IMMUNOCONJUGATES; MAYTANSINE; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; POLYSACCHARIDES; PROTEIN STABILITY; TRASTUZUMAB;

EID: 84945366854     PISSN: 10431802     EISSN: 15204812     Source Type: Journal    
DOI: 10.1021/acs.bioconjchem.5b00224     Document Type: Article

References (43)

1. Mathé, G., Loc, T. B., and Bernard, J. (1958) Effet sur la leucémie 1210 de la souris d'une combinaison par diazotation d'A-méthoptérine et de γ-globulines de hamsters porteurs de cette leucémie par hétérogreffe Compt. Rendu Acad. Sci. (Paris) 246, 1626-8
2. Himmelweit, F. (1960) The Collected Papers of Paul Ehrlich, p 59, Vol. 3, Pergamon, London.
3. Chari, R. V. J., Miller, M. L., and Widdison, W. C. (2014) Antibody-Drug Conjugates: An Emerging Concept in Cancer Therapy Angew. Chem., Int. Ed. 53, 3796-827
4. Junutula, J. R., Raab, H., Clark, S., Bhakta, S., Leipold, D. D., Weir, S., Chen, Y., Simpson, M., Tsai, S. P., Dennis, M. S., Lu, Y., Meng, Y. G., Ng, C., Yang, J., Lee, C. C., Duenas, E., Gorrell, J., Katta, V., Kim, A., McDorman, K., Flagella, K., Venook, R., Ross, S., Spencer, S. D., Wong, W. L., Lowman, H. B., Vandlen, R., Sliwkowski, M. X., Scheller, R. H., Polakis, P., and Mallet, M. (2008) Site-specific conjugation of a cytotoxic drug to an antibody improves the therapeutic index Nat. Biotechnol. 26, 925-32
5. Krop, I. E., Beeram, M., Modi, S., Jones, S. F., Holden, S. N., Yu, W., Girish, S., Tibbitts, J., Yi, J.-H., Sliwkowski, M. X., Jacobson, F., Lutzker, S. G., and Burris, H. A. (2010) Phase I study of trastuzumab-DM1, an HER2 antibody-drug conjugate, given every 3 weeks to patients with HER2-positive metastatic breast cancer J. Clin. Oncol. 28, 2698-704
6. Beeram, M., Krop, I. E., Burris, H. A., Girish, S. R., Yu, W., Lu, M. W., Holden, S. N., and Modi, S. (2012) A phase 1 study of weekly dosing of trastuzumab emtansine (T-DM1) in patients with advanced human epidermal growth factor 2-positive breast cancer Cancer 118, 5733-40
7. Shen, B.-Q., Xu, K., Liu, L., Raab, H., Bhakta, S., Kenrick, M., Parsons-Reponte, K. L., Tien, J., Yu, S.-F., Mai, E., Li, D., Tibbitts, J., Baudys, J., Saad, O. M., Scales, S. J., McDonald, P. J., Hass, P. E., Eigenbrot, C., Nguyen, T., Solis, W. A., Fuji, R. N., Flagella, K. M., Patel, D., Spencer, S. D., Khawli, L. A., Ebens, A., Wong, W. L., Vandlen, R., Kaur, S., Sliwkowski, M. X., Scheller, R. H., Polakis, P., and Junutula, J. R. (2012) Conjugation site modulates the in vivo stability and therapeutic activity of antibody-drug conjugates Nat. Biotechnol. 30, 184-9
8. Lyon, R. P., Setter, J. R., Bovee, T. D., Doronina, S. O., Hunter, J. H., Anderson, M. E., Balasubramanian, C. L., Duniho, S. M., Leiske, C. I., Li, F., and Senter, P. D. (2014) Self-hydrolyzing maleimides improve the stability and pharmacological properties of antibody-drug conjugates Nat. Biotechnol. 32, 1059-1062
9. Tumey, L. N., Charati, M., He, T., Sousa, E., Ma, D., Han, X., Clark, T., Casavant, J., Loganzo, F., Barletta, F., Lucas, J., and Graziani, E. I. (2014) Mild method for succinimide hydrolysis on ADCs: impact on ADC potency, stability, exposure, and efficacy Bioconjugate Chem. 25, 1871-80
10. Aggerwal, P. and Bertozzi, C. R. (2014) Site-specific antibody-drug conjugates: the nexus of bioorthogonal chemistry, protein engineering, and drug development Bioconjugate Chem. 53, 176-92
11. For example, an extensive optimization process to avoid formation of triple light chain antibody format of a THIOmab did not afford titers above 2 g/L, whereas for regular IgG yields of 3-5 g/L are customary. Gomez, N., Ouyang, J., Nguyen, M. D. H., Vinson, A. R., Lin, A. A., and Yuk, I. H. (2010) Effect of temperature, pH, dissolved oxygen, and hydrolysate on the formation of triple light chain antibodies in cell culture Biotechnol. Prog. 26, 1438-45
12. Tian, F., Lu, Y., Manibusan, A., Sellers, A., Tran, H., Sun, Y., Phuong, T., Barnett, R., Hehli, B., Song, F., DeGuzman, M. J., Ensari, S., Pinkstaff, J. K., Sullivan, L. M., Biroc, S. L., Cho, H., Schultz, P. G., DiJoseph, J., Dougher, M., Ma, D., Dushin, R., Leal, M., Tchistiakova, L., Feyfant, E., Gerber, H. P., and Sapra, P. (2014) A general approach to site-specific antibody drug conjugates Proc. Natl. Acad. Sci. U. S. A. 111, 1766-71
13. Zimmerman, E. S., Heibeck, T. H., Gill, A., Li, X., Murray, C. J., Madlansacay, M. R., Tran, C., Uter, N. T., Yin, G., Rivers, P. J., Yam, A. Y., Wang, W. D., Steiner, A. R., Bajad, S. U., Penta, K., Yang, W., Hallam, T. J., Thanos, C. D., and Sato, A. K. (2014) Production of site-specific antibody-drug conjugates using optimized non-natural amino acids in a cell-free expression system Bioconjugate Chem. 25, 351-61
14. Fontaine, S. D., Reid, R., Robinson, L., Ashley, G. W., and Santi, D. V. (2014) Long-term stabilization of maleimide-thiol conjugates Bioconjugate Chem. 26, 145-52
15. Beck, A., Wagner-Rousset, E., Ayoub, D., Van Dorsselaer, A., and Sanglier-Cianférani, S. (2013) Characterization of therapeutic antibodies and related products Anal. Chem. 85, 715-36
16. Goetze, A. M., Liu, Y. D., Zhang, Z., Shah, B., Lee, E., Bondarenko, P. V., and Flynn, G. C. (2011) High-mannose glycans on the Fc region of therapeutic IgG antibodies increase serum clearance in humans Glycobiology 21, 949-59
17. Ferrara, C., Grau, S., Jäger, C., Sondermann, P., Brünker, P., Waldhauer, I., Hennig, M., Ruf, A., Rufer, A. C., Stihle, M., Umaña, P., and Benz, J. (2011) Unique carbohydrate-carbohydrate interactions are required for high affinity binding between FcgammaRIII and antibodies lacking core fucose Proc. Natl. Acad. Sci. U. S. A. 108, 12669-74
18. For example, see discussion in Sazinsky, S. L., Ott, R. G., Silver, N. W., Tidor, B., Ravetch, J. V., and Wittrup, K. D. (2008) Aglycosylated immunoglobulin G1 variants productively engage activating Fc receptors. Proc. Natl. Acad. Sci. U.S.A. 105, 20167-72.
19. Gorovits, B. and Krinos-Fiorotti, C. (2013) Proposed mechanism of off-target toxicity for antibody-drug conjugates driven by mannose receptor uptake Cancer Immunol. Immunother. 62, 217-23
20. Qu, Z., Sharkey, R. M., Hansen, H. J., Shih, L. B., Govindan, S. V., Shen, J., Goldenberg, D. M., and Leung, S. (1998) Carbohydrates engineered at antibody constant domains can be used for site-specific conjugation of drugs and chelates J. Immunol. Meth. 213, 131-44
21. Boeggeman, E., Ramakrishnan, B., Pasek, M., Manzoni, M., Puri, A., Loomis, K. H., Waybright, T. J., and Qasba, P. K. (2009) Site specific conjugation of fluoroprobes to the remodeled Fc N-glycans of monoclonal antibodies using mutant glycosyltransferases: application for cell-surface antigen detection Bioconjugate Chem. 20, 1228-36
22. Zhu, Z., Ramakrishnan, B., Li, J., Wang, Y., Feng, Y., Prabakaran, P., Colantonio, S., Dyba, M. A., Qasba, P. K., and Dimitrov, D. S. (2014) Site-specific antibody-drug conjugation through an engineered glycotransferase and a chemically reactive sugar mAbs 6, 1-11
23. Zeglis, B. M., Davis, C. B., Aggeler, R., Kang, H.-C., Chen, A., Agnew, B., and Lewis, J. S. (2013) An enzyme-mediated methodology for the site-specific radiolabeling of antibodies based on catalyst-free click chemistry Bioconjugate Chem. 24, 1057-67
24. Li, X., Fang, T., and Boons, G.-J. (2014) Preparation of well-defined antibody-drug conjugates through glycan remodeling and strain-promoted azide-alkyne cycloadditions Angew. Chem., Int. Ed. 53, 7179-82
25. For an overview of different endo F glycosidase, see for example: http://www.sigmaaldrich.com/technical-documents/articles/biology/glycobiology/endoglycosidases.html (accessed on April 20th, 2015).
26. Also, see the following review: Karamanos, Y. (2013) Endo-N-acetyl-β-D-glucosaminidases and peptide-N4-(N-acetyl-β-D-glucosaminyl) asparagineamidases: More than just tools Adv. Biochem. 1, 81-99
27. Colin, M. and Olsen, A. (2001) EndoS, a novel secreted protein from Streptococcus pyogenes with endoglycosidase activity on human IgG EMBO J. 20, 3046-55
28. Goodfellow, J. J., Baruah, K., Yamamoto, K., Bonomelli, C., Krishna, B., Harvey, D. J., Crispin, M., Scanlan, C. N., and Davis, B. G. (2012) An endoglycosidase with alternative glycan specificity allows broadened glycoprotein remodelling J. Am. Chem. Soc. 134, 8030-3
29. Sjögren, J., Struwe, W. B., Cosgrave, E. F. J., Rudd, P. M., Stervander, M., Allhorn, M., Hollands, A., Nizet, V., and Collin, M. (2013) EndoS2 is a unique and conserved enzyme of serotype M49 group A Streptococcus that hydrolyses N-linked glycans on IgG and α1-acid glycoprotein Biochem. J. 455, 107-18
30. Ramakrishnan, B. and Qasba, P. K. (2002) Structure-based design of β1,4-galactosyltransferase I (β4Gal-T1) with equally efficient N-acetylgalactosaminyltransferase activity J. Biol. Chem. 277, 20833-9
31. Khidekel, N., Arndt, S., Lamarre-Vincent, N., Lippert, A., Poulin-Kerstien, K. G., Ramakrishnan, B., Qasba, P. K., and Hsieh-Wilson, L. C. (2003) A chemoenzymatic approach toward the rapid and sensitive detection of O-GlcNAc posttranslational modifications J. Am. Chem. Soc. 125, 16162-3
32. Hang, H. C., Yu, C., Pratt, M. R., and Bertozzi, C. R. (2004) Probing glycosyltransferase activities with the Staudinger ligation J. Am. Chem. Soc. 126, 6-7
33. Agard, N. J., Prescher, J. A., and Bertozzi, C. R. (2004) A strain-promoted [3 + 2] azide-alkyne cycloaddition for covalent modification of biomolecules in living systems J. Am. Chem. Soc. 126, 15046-7
34. Debets, M. F., van Berkel, S. S., Dommerholt, J., Dirks, A. J., Rutjes, F. P. J. T., and van Delft, F. L. (2011) Bioconjugation with strained alkenes and alkynes Acc. Chem. Res. 44, 805-15
35. Dommerholt, J., Schmidt, S., Temming, R., Hendriks, L. J., Rutjes, F. P. J. T., van Hest, J. C. M., Lefeber, D. J., Friedl, P., and van Delft, F. L. (2010) Readily accessible bicyclononynes for bioorthogonal labeling and three-dimensional imaging of living cells Angew. Chem., Int. Ed. 49, 9422-5
36. Debets, M. F., van Berkel, S. S., Schoffelen, S., Rutjes, F. P. J. T., van Hest, J. C. M., and van Delft, F. L. (2010) Aza-dibenzocyclooctynes for fast and efficient enzyme PEGylation via copper-free (3 + 2) cycloaddition Chem. Commun. 46, 97-9
37. Jung, S. T., Reddy, S. T., Kang, T. H., Borrok, M. J., Sandlie, I., Tucker, P. W., and Georgiou, G. (2010) A glycosylated IgG variants expressed in bacteria that selectively bind FcγRI potentiate tumour cell killing by monocyte-dendritic cells Proc. Natl. Acad. Sci. U.S.A. 201, 604-9
38. Dommerholt, J., van Rooijen, O., Borrmann, A., Fonseca Guerra, C., Bickelhaupt, F. M., and van Delft, F. L. (2014) Highly accelerated inverse electron-demand cycloaddition of electron-deficient azides with aliphatic cyclooctynes. Nat. Commun. 5, DOI: 10.1038/ncomms6378.
39. Strop, P., Liu, S. H., Dorywalska, M., Delaria, K., Dushin, R. G., Tran, T. T., Ho, W. H., Farias, S., Casas, M. G., Abdiche, Y., Zhou, D., Chandrasekaran, R., Samain, C., Loo, C., Rossi, A., Rickert, M., Krimm, S., Wong, T., Chin, S. M., Yu, J., Dilley, J., Chaparro-Riggers, J., Filzen, G. F., O'Donnell, C. J., Wang, F., Myers, J. S., Pons, J., Shelton, D. L., and Rajpal, A. (2013) Location matters: site of conjugation modulates stability and pharmacokinetics of antibody drug conjugates Chem. Biol. 20, 161-7
40. Dorywalska, M., Strop, P., Melton-Witt, J. A., Hasa-Moreno, A., Farias, S. E., Galindo Casas, M., Delaria, K., Lui, V., Poulsen, K., Loo, C., Krimm, S., Bolton, G., Moine, L., Dushin, R., Tran, T.-T., Liu, S.-H., Rickert, M., Foletti, D., Shelton, D. L., Pons, J., and Rajpal, A. (2015) Effect of attachment site on stability of cleavable antibody drug conjugates Bioconjugate Chem. 10.1021/bc5005747
41. Masuko, S., Bero, S., Green, D. E., Weïwer, M., Liu, J., DeAngelis, P. L., and Linhardt, R. J. (2012) Chemoenzymatic synthesis of uridine diphosphate-GlcNAc and uridine diphosphate-GalNAc analogs for the preparation of unnatural glycosaminoglycans J. Org. Chem. 77, 1449-56
42. Baisch, G. and Öhrlein, R. (1997) Convenient chemoenzymatic synthesis of β-purine-diphosphate sugars (GDP-fucose-analogues) Bioorg. Med. Chem. 5, 383-91
43. Boeggeman, E. E., Ramakrishnan, B., and Qasba, P. K. (2003) The N-terminal stem region of bovine and human β-1,4-galactosyltransferase I increases the in vitro folding efficiency of their catalytic domain from inclusion bodies Protein Expression Purif. 30, 219-29