3,423
Views
0
CrossRef citations to date
0
Altmetric
Report

Nonclinical immunogenicity risk assessment for knobs-into-holes bispecific IgG1 antibodies

ORCID Icon, ORCID Icon, , , ORCID Icon, , ORCID Icon, , , ORCID Icon, ORCID Icon, ORCID Icon, , ORCID Icon, ORCID Icon & ORCID Icon show all
Article: 2362789 | Received 15 Feb 2024, Accepted 29 May 2024, Published online: 06 Jun 2024

References

  • The Antibody Society. Therapeutic monoclonal antibodies approved or in regulatory review. [accessed 2024 May 31]. www.antibodysociety.org/antibody-therapeutics-product-data.
  • Labrijn AF, Janmaat ML, Reichert JM, Parren P. Bispecific antibodies: a mechanistic review of the pipeline. Nat Rev Drug Discov. 2019;18(8):585–16. doi:10.1038/s41573-019-0028-1.
  • Li Y. A brief introduction of IgG-like bispecific antibody purification: Methods for removing product-related impurities. Protein Expr Purif. 2019;155:112–19. doi:10.1016/j.pep.2018.11.011.
  • Atwell S, Ridgway JB, Wells JA, Carter P. Stable heterodimers from remodeling the domain interface of a homodimer using a phage display library. J Mol Biol. 1997;270(1):26–35. doi:10.1006/jmbi.1997.1116.
  • Merchant AM, Zhu Z, Yuan JQ, Goddard A, Adams CW, Presta LG, Carter P. An efficient route to human bispecific IgG. Nat Biotechnol. 1998;16(7):677–81. doi:10.1038/nbt0798-677.
  • Ridgway JB, Presta LG, Carter P. ‘Knobs-into-holes’ engineering of antibody CH domains for heavy chain heterodimerization. Protein Eng Des Sel. 1996;9(7):617–21. doi:10.1093/protein/9.7.617.
  • Spiess C, Merchant M, Huang A, Zheng Z, Yang NY, Peng J, Ellerman D, Shatz W, Reilly D, Yansura DG. et al. Bispecific antibodies with natural architecture produced by co-culture of bacteria expressing two distinct half-antibodies. Nat Biotechnol. 2013;31(8):753–58. doi:10.1038/nbt.2621.
  • Dillon M, Yin Y, Zhou J, McCarty L, Ellerman D, Slaga D, Junttila TT, Han G, Sandoval W, Ovacik MA. et al. Efficient production of bispecific IgG of different isotypes and species of origin in single mammalian cells. Mabs-austin. 2017;9(2):213–30. doi:10.1080/19420862.2016.1267089.
  • Hellmann MD, Bivi N, Calderon B, Shimizu T, Delafontaine B, Liu ZT, Szpurka AM, Copeland V, Hodi FS, Rottey S. et al. Safety and immunogenicity of LY3415244, a bispecific antibody against TIM-3 and PD-L1, in patients with advanced solid tumors. Clin Cancer Res. 2021;27(10):2773–81. doi:10.1158/1078-0432.Ccr-20-3716.
  • Akpalu DE, Frederick B, Nnane IP, Yao Z, Shen F, Ort T, Fink D, Dogmanits S, Raible D, Sharma A. et al. Pharmacokinetics, pharmacodynamics, immunogenicity, safety, and tolerability of JNJ-61178104, a novel tumor necrosis factor-alpha and interleukin-17A bispecific antibody, in healthy subjects. J Clin Pharmacol. 2019;59(7):968–78. doi:10.1002/jcph.1393.
  • US Food and Drug Administration. Highlights of prescribing information, RYBREVANT (amivantamab-vmjw) injection, for intravenous use. [accessed 2023 June 8]. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761210s000lbl.pdf.
  • Schmitt C, Emrich T, Chebon S, Fernandez E, Petry C, Yoneyama K, Kiialainen A, Howard M, Niggli M, Paz-Priel I. et al. Low immunogenicity of emicizumab in persons with haemophilia a. Haemophilia. 2021;27(6):984–92. doi:10.1111/hae.14398.
  • Kroenke MA, Milton MN, Kumar S, Bame E, White JT. Immunogenicity risk assessment for multi-specific therapeutics. Aaps J. 2021;23(6):115. doi:10.1208/s12248-021-00642-5.
  • Zhou Y, Penny HL, Kroenke MA, Bautista B, Hainline K, Chea LS, Parnes J, Mytych DT. Immunogenicity assessment of bispecific antibody-based immunotherapy in oncology. J Immunother Cancer. 2022;10(4):e004225. doi:10.1136/jitc-2021-004225.
  • Sampei Z, Igawa T, Soeda T, Okuyama-Nishida Y, Moriyama C, Wakabayashi T, Tanaka E, Muto A, Kojima T, Kitazawa T. et al. Identification and multidimensional optimization of an asymmetric bispecific IgG antibody mimicking the function of factor VIII cofactor activity. PLoS One. 2013;8(2):e57479. doi:10.1371/journal.pone.0057479.
  • Tourdot S, Hickling TP. Nonclinical immunogenicity risk assessment of therapeutic proteins. Bioanal. 2019;11(17):1631–43. doi:10.4155/bio-2018-0246.
  • Ducret A, Ackaert C, Bessa J, Bunce C, Hickling T, Jawa V, Kroenke MA, Lamberth K, Manin A, Penny HL. et al. Assay format diversity in pre-clinical immunogenicity risk assessment: Toward a possible harmonization of antigenicity assays. Mabs-austin. 2022;14(1):1993522. doi:10.1080/19420862.2021.1993522.
  • Ulitzka M, Carrara S, Grzeschik J, Kornmann H, Hock B, Kolmar H. Engineering therapeutic antibodies for patient safety: tackling the immunogenicity problem. Prot Eng Des Sel. 2020;33. doi:10.1093/protein/gzaa025.
  • Harris CT, Cohen S. Reducing immunogenicity by design: approaches to minimize immunogenicity of monoclonal antibodies. BioDrugs. 2024;38(2):205–26. doi:10.1007/s40259-023-00641-2.
  • Arata Y, Motoyama S, Yano M, Ikuno T, Ito S, Matsushita T, Takeiri A, Nishito Y, Yabuki N, Mizuno H. et al. Rapid in vitro assessment of the immunogenicity potential of engineered antibody therapeutics through detection of CD4(+) T cell interleukin-2 secretion. Mabs-austin. 2023;15(1):2253570. doi:10.1080/19420862.2023.2253570.
  • Abbas AK, Lichtman AH, Pillai S. Cellular and Molecular Immunology. In: Bowes J, editor. Cellular and Molecular Immunology. 10th ed. Philadelphia, PA: Elsevier; 2021. p. 261–285, 337–363.
  • Cassotta A, Mikol V, Bertrand T, Pouzieux S, Le Parc J, Ferrari P, Dumas J, Auer M, Deisenhammer F, Gastaldi M. et al. A single T cell epitope drives the neutralizing anti-drug antibody response to natalizumab in multiple sclerosis patients. Nat Med. 2019;25(9):1402–07. doi:10.1038/s41591-019-0568-2.
  • Cia G, Pucci F, Rooman M. Critical review of conformational B-cell epitope prediction methods. Brief Bioinform. 2023;24(1). doi:10.1093/bib/bbac567.
  • Lin J, Lee SL, Russell AM, Huang RF, Batt MA, Chang SS, Ferrante A, Verdino P, Henry KA. A structure-based engineering approach to abrogate pre-existing antibody binding to biotherapeutics. PLoS One. 2021;16(7):e0254944. doi:10.1371/journal.pone.0254944.
  • Cohen S, Chung S, Spiess C, Lundin V, Stefanich E, Laing ST, Clark V, Brumm J, Zhou Y, Huang C. et al. An integrated approach for characterizing immunogenic responses toward a bispecific antibody. Mabs-austin. 2021;13(1):1944017. doi:10.1080/19420862.2021.1944017.
  • Peng K, Siradze K, Fischer SK. Characterization of robust immune responses to a bispecific antibody, a novel class of antibody therapeutics. Bioanal. 2021;13(4):239–52. doi:10.4155/bio-2020-0281.
  • Schick AJ 3rd, Lundin V, Low J, Peng K, Vandlen R, Wecksler AT. Epitope mapping of anti-drug antibodies to a clinical candidate bispecific antibody. Mabs-austin. 2022;14(1):2028337. doi:10.1080/19420862.2022.2028337.
  • US Food and Drug Administration. Highlights of prescribing information, AVASTIN (bevacizumab) injection, for intravenous use. [accessed 2023 Jul 31]. www.accessdata.fda.gov/drugsatfda_docs/label/2017/761083s000lbl.pdf.
  • US Food and Drug Administration. Highlights of prescribing information, HERCEPTIN HYLECTA™ (trastuzumab and hyaluronidase-oysk) injection, for subcutaneous use. [accessed 2023 June 8]. www.accessdata.fda.gov/drugsatfda_docs/label/2022/761235s000lbl.pdf.
  • Jackisch C, Kim SB, Semiglazov V, Melichar B, Pivot X, Hillenbach C, Stroyakovskiy D, Lum BL, Elliott R, Weber HA. et al. Subcutaneous versus intravenous formulation of trastuzumab for HER2-positive early breast cancer: updated results from the phase III HannaH study. Ann Oncol. 2015;26(2):320–25. doi:10.1093/annonc/mdu524.
  • Merchant M, Ma X, Maun HR, Zheng Z, Peng J, Romero M, Huang A, Yang NY, Nishimura M, Greve J. et al. Monovalent antibody design and mechanism of action of onartuzumab, a MET antagonist with anti-tumor activity as a therapeutic agent. Proc Natl Acad Sci U S A. 2013;110(32):E2987–2996. doi:10.1073/pnas.1302725110.
  • Salgia R, Patel P, Bothos J, Yu W, Eppler S, Hegde P, Bai S, Kaur S, Nijem I, Catenacci DV. et al. Phase I dose-escalation study of onartuzumab as a single agent and in combination with bevacizumab in patients with advanced solid malignancies. Clin Cancer Res. 2014;20(6):1666–75. doi:10.1158/1078-0432.Ccr-13-2070.
  • Xin Y, Jin D, Eppler S, Damico-Beyer LA, Joshi A, Davis JD, Kaur S, Nijem I, Bothos J, Peterson A. et al. Population pharmacokinetic analysis from phase I and phase II studies of the humanized monovalent antibody, onartuzumab (MetMab), in patients with advanced solid tumors. J Clin Pharmacol. 2013;53(11):1103–11. doi:10.1002/jcph.148.
  • Ridker PM, Tardif JC, Amarenco P, Duggan W, Glynn RJ, Jukema JW, Kastelein JJP, Kim AM, Koenig W, Nissen S. et al. Lipid-reduction variability and antidrug-antibody formation with bococizumab. N Engl J Med. 2017;376(16):1517–26. doi:10.1056/NEJMoa1614062.
  • Hua F, Comer GM, Stockert L, Jin B, Nowak J, Pleasic-Williams S, Wunderlich D, Cheng J, Beebe JS. Anti-IL21 receptor monoclonal antibody (ATR-107): safety, pharmacokinetics, and pharmacodynamic evaluation in healthy volunteers: a phase I, first-in-human study. J Clin Pharmacol. 2014;54(1):14–22. doi:10.1002/jcph.158.
  • Melendez R, Ordonia B, Guerrero J, Hassanzadeh A, Tran P, Low J, Wong M, Brumm J, Chung S, Kamen L. Introducing dendritic cell antibody internalization as an immunogenicity risk assessment tool. Bioanal. 2022;14(10):703–13. doi:10.4155/bio-2022-0024.
  • Reynisson B, Alvarez B, Paul S, Peters B, Nielsen M. NetMHCpan-4.1 and NetMHCIIpan-4.0: improved predictions of MHC antigen presentation by concurrent motif deconvolution and integration of MS MHC eluted ligand data. Nucleic Acids Res. 2020;48(W1):W449–54. doi:10.1093/nar/gkaa379.
  • Quarmby V, Phung QT, Lill JR. MAPPs for the identification of immunogenic hotspots of biotherapeutics; an overview of the technology and its application to the biopharmaceutical arena. Expert Rev Proteomics. 2018;15(9):733–48. doi:10.1080/14789450.2018.1521279.
  • Sekiguchi N, Kubo C, Takahashi A, Muraoka K, Takeiri A, Ito S, Yano M, Mimoto F, Maeda A, Iwayanagi Y. et al. MHC-associated peptide proteomics enabling highly sensitive detection of immunogenic sequences for the development of therapeutic antibodies with low immunogenicity. Mabs-austin. 2018;10(8):1168–81. doi:10.1080/19420862.2018.1518888.
  • Cohen S, Myneni S, Batt A, Guerrero J, Brumm J, Chung S. Immunogenicity risk assessment for biotherapeutics through in vitro detection of CD134 and CD137 on T helper cells. Mabs-austin. 2021;13(1):1898831. doi:10.1080/19420862.2021.1898831.
  • Ito S, Ikuno T, Mishima M, Yano M, Hara T, Kuramochi T, Sampei Z, Wakabayashi T, Tabo M, Chiba S. et al. In vitro human helper T-cell assay to screen antibody drug candidates for immunogenicity. J Immunotoxicol. 2019;16(1):125–32. doi:10.1080/1547691X.2019.1604586.
  • Marrama D, Chronister WD, Westernberg L, Vita R, Kosaloglu-Yalcin Z, Sette A, Nielsen M, Greenbaum JA, Peters B. PEPMatch: a tool to identify short peptide sequence matches in large sets of proteins. BMC Bioinf. 2023;24(1):485. doi:10.1186/s12859-023-05606-4.
  • Kovaltsuk A, Leem J, Kelm S, Snowden J, Deane CM, Krawczyk K. Observed antibody space: a resource for data mining next-generation sequencing of antibody repertoires. J Immunol. 2018;201(8):2502–09. doi:10.4049/jimmunol.1800708.
  • Olsen TH, Boyles F, Deane CM. Observed antibody space: A diverse database of cleaned, annotated, and translated unpaired and paired antibody sequences. Protein Sci. 2022;31(1):141–46. doi:10.1002/pro.4205.
  • Prihoda D, Maamary J, Waight A, Juan V, Fayadat-Dilman L, Svozil D, DA B. BioPhi: A platform for antibody design, humanization, and humanness evaluation based on natural antibody repertoires and deep learning. Mabs-austin. 2022;14(1):2020203. doi:10.1080/19420862.2021.2020203.
  • Egholm Bruun Jensen E, Reynisson B, Barra C, Nielsen M. New light on the HLA-DR immunopeptidomic landscape. J Leukoc Biol. 2024;115(5):913–25. doi:10.1093/jleuko/qiae007.
  • Wen Y, Cahya S, Zeng W, Lin J, Wang X, Liu L, Malherbe L, Siegel R, Ferrante A, Kaliyaperumal A. Development of a FRET-based assay for analysis of mAbs internalization and processing by dendritic cells in preclinical immunogenicity risk assessment. Aaps J. 2020;22(3):68. doi:10.1208/s12248-020-00444-1.
  • Gokemeijer J, Wen Y, Jawa V, Mitra-Kaushik S, Chung S, Goggins A, Kumar S, Lamberth K, Liao K, Lill J. et al. Survey outcome on immunogenicity risk assessment tools for biotherapeutics: an insight into consensus on methods, application, and utility in drug development. Aaps J. 2023;25(4):55. doi:10.1208/s12248-023-00820-7.
  • Xue L, Hickling T, Song R, Nowak J, Rup B. Contribution of enhanced engagement of antigen presentation machinery to the clinical immunogenicity of a human interleukin (IL)-21 receptor-blocking therapeutic antibody. Clin Exp Immunol. 2016;183(1):102–13. doi:10.1111/cei.12711.
  • Spindeldreher S, Karle A, Correia E, Tenon M, Gottlieb S, Huber T, Maillere B, Kolbinger F. T cell epitope mapping of secukinumab and ixekizumab in healthy donors. Mabs-austin. 2020;12(1):1707418. doi:10.1080/19420862.2019.1707418.
  • Hartman K, Steiner G, Siegel M, Looney CM, Hickling TP, Bray-French K, Springer S, Marban-Doran C, Ducret A. Expanding the MAPPs assay to accommodate MHC-II pan receptors for improved predictability of potential T cell epitopes. Biology. 2023;12(9):1265. doi:10.3390/biology12091265.
  • Moussa EM, Panchal JP, Moorthy BS, Blum JS, Joubert MK, Narhi LO, Topp EM. Immunogenicity of therapeutic protein aggregates. J Pharm Sci. 2016;105(2):417–30. doi:10.1016/j.xphs.2015.11.002.
  • Ratanji KD, Derrick JP, Dearman RJ, Kimber I. Immunogenicity of therapeutic proteins: influence of aggregation. J Immunotoxicol. 2014;11(2):99–109. doi:10.3109/1547691X.2013.821564.
  • Dyson MR, Masters E, Pazeraitis D, Perera RL, Syrjanen JL, Surade S, Thorsteinson N, Parthiban K, Jones PC, Sattar M. et al. Beyond affinity: selection of antibody variants with optimal biophysical properties and reduced immunogenicity from mammalian display libraries. Mabs-austin. 2020;12(1):1829335. doi:10.1080/19420862.2020.1829335.
  • Jain T, Boland T, Lilov A, Burnina I, Brown M, Xu Y, Vasquez M, Valencia A. Prediction of delayed retention of antibodies in hydrophobic interaction chromatography from sequence using machine learning. Bioinformatics. 2017;33(23):3758–66. doi:10.1093/bioinformatics/btx519.
  • Jain T, Boland T, Vasquez M. Identifying developability risks for clinical progression of antibodies using high-throughput in vitro and in silico approaches. Mabs-austin. 2023;15(1):2200540. doi:10.1080/19420862.2023.2200540.
  • Bostrom J, Yu SF, Kan D, Appleton BA, Lee CV, Billeci K, Man W, Peale F, Ross S, Wiesmann C. et al. Variants of the antibody herceptin that interact with HER2 and VEGF at the antigen binding site. Science. 2009;323(5921):1610–14. doi:10.1126/science.1165480.
  • Hill AG, Findlay MP, Burge ME, Jackson C, Alfonso PG, Samuel L, Ganju V, Karthaus M, Amatu A, Jeffery M. et al. Phase II study of the dual EGFR/HER3 inhibitor duligotuzumab (MEHD7945A) versus cetuximab in combination with FOLFIRI in second-line RAS wild-type metastatic colorectal cancer. Clin Cancer Res. 2018;24(10):2276–84. doi:10.1158/1078-0432.CCR-17-0646.
  • Fayette J, Wirth L, Oprean C, Udrea A, Jimeno A, Rischin D, Nutting C, Harari PM, Csoszi T, Cernea D. et al. Randomized phase II study of duligotuzumab (MEHD7945A) vs. cetuximab in squamous cell carcinoma of the head and neck (MEHGAN Study). Front Oncol. 2016;6:232. doi:10.3389/fonc.2016.00232.
  • Beckmann R, Jensen K, Fenn S, Speck J, Krause K, Meier A, Roth M, Fauser S, Kimbung R, Logan DT. et al. DutaFabs are engineered therapeutic Fab fragments that can bind two targets simultaneously. Nat Commun. 2021;12(1):708. doi:10.1038/s41467-021-20949-3.
  • Kabat EA, Wu TT, Perry HM, Gottesman KS, Foeller C. Sequences of proteins of immunological interest. 5th ed. Bethesda (MD): NIH; 1991.
  • Edelman GM, Cunningham BA, Gall WE, Gottlieb PD, Rutishauser U, Waxdal MJ. The covalent structure of an entire gammaG immunoglobulin molecule. Proc Natl Acad Sci U S A. 1969;63(1):78–85. doi:10.1073/pnas.63.1.78.
  • Swaminathan A, Lucas RM, Dear K, McMichael AJ. Keyhole limpet haemocyanin - a model antigen for human immunotoxicological studies. Br J Clin Pharmacol. 2014;78(5):1135–42. doi:10.1111/bcp.12422.