Non-immunoglobulin synthetic binding proteins for oncology

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

Extensive application of technologies like phage display in screening peptide and protein combinatorial libraries has not only facilitated creation of new recombinant antibodies but has also significantly enriched repertoire of the protein binders that have polypeptide scaffolds without homology to immunoglobulins. These innovative synthetic binding protein (SBP) platforms have grown in number and now encompass monobodies/adnectins, DARPins, lipocalins/anticalins, and a variety of miniproteins such as affibodies and knottins, among others. They serve as versatile modules for developing complex affinity tools that hold promise in both diagnostic and therapeutic settings. An optimal scaffold typically has low molecular weight, minimal immunogenicity, and demonstrates resistance against various challenging conditions, including proteolysis - making it potentially suitable for peroral administration. Retaining functionality under reducing intracellular milieu is also advantageous. However, paramount to its functionality is the scaffold’s ability to tolerate mutations across numerous positions, allowing for the formation of a sufficiently large target binding region. This is achieved through the library construction, screening, and subsequent expression in an appropriate system. Scaffolds that exhibit high thermodynamic stability are especially coveted by the developers of new SBPs. These are steadily making their way into clinical settings, notably as antagonists of oncoproteins in signaling pathways. This review surveys the diverse landscape of SBPs, placing particular emphasis on the inhibitors targeting the oncoprotein KRAS, and highlights groundbreaking opportunities for SBPs in oncology.

About the authors

T. I David

Institute of Biomedical Chemistry;Phystech School of Biological and Medical Physics, Moscow Institute of Physics and Technology

119121 Moscow, Russia;=141701 Dolgoprudny, Moscow Region, Russia

N. B Pestov

Institute of Biomedical Chemistry;Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products, Russian Academy of Sciences;Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry

Email: nayeoff@yahoo.com
119121 Moscow, Russia;=108819 Moscow, Russia;=117997 Moscow, Russia

T. V Korneenko

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry

=117997 Moscow, Russia

N. A Barlev

Institute of Biomedical Chemistry;Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products, Russian Academy of Sciences;Institute of Cytology, Russian Academy of Sciences;Nazarbayev University

119121 Moscow, Russia;=108819 Moscow, Russia;=194064 St.-Petersburg, Russia;=010000 Astana, Kazakhstan

References

  1. Weidle, U. H., Auer, J., Brinkmann, U., Georges, G., and Tiefenthaler, G. (2013) The emerging role of new protein scaffold-based agents for treatment of cancer, Cancer Genomics Proteomics, 10, 155-168.
  2. Rabia, L. A., Desai, A. A., Jhajj, H. S., and Tessier, P. M. (2018) Understanding and overcoming trade-offs between antibody affinity, specificity, stability and solubility, Biochem. Eng. J., 137, 365-374, doi: 10.1016/j.bej.2018.06.003.
  3. Cunningham, O., Scott, M., Zhou, Z. S., and Finlay, W. J. J. (2021) Polyreactivity and polyspecificity in therapeutic antibody development: risk factors for failure in preclinical and clinical development campaigns, MAbs, 13, 1999195, doi: 10.1080/19420862.2021.1999195.
  4. Van Regenmortel, M. H. V. (2014) Specificity, polyspecificity, and heterospecificity of antibody-antigen recognition, J. Mol. Recognit., 27, 627-639, doi: 10.1002/jmr.2394.
  5. Пестов Н. Б., Гусакова Т. В., Костина М. Б., Шахпаронов М. И. (1996) Фаговые мимотопы моноклональных антител к Ca2+-ATP-азе плазматических мембран, Биоорг. Хим., 22, 664.
  6. Rabia, L. A., Zhang, Y., Ludwig, S. D., Julian, M. C., and Tessier, P. M. (2018) Net charge of antibody complementarity-determining regions is a key predictor of specificity, Protein Eng. Des. Sel., 31, 409-418, doi: 10.1093/protein/gzz002.
  7. Gebauer, M., and Skerra, A. (2020) Engineered protein scaffolds as next-generation therapeutics, Annu. Rev. Pharmacol. Toxicol., 60, 391-415, doi: 10.1146/annurev-pharmtox-010818-021118.
  8. Aguilar, G., Vigano, M. A., Affolter, M., and Matsuda, S. (2019) Reflections on the use of protein binders to study protein function in developmental biology, Wiley Interdiscip. Rev. Dev. Biol., 8, e356, doi: 10.1002/wdev.356.
  9. Jenkins, T. P., Fryer, T., Dehli, R. I., Jürgensen, J. A., Fuglsang-Madsen, A., et al. (2019) Toxin neutralization using alternative binding proteins, Toxins (Basel), 11, E53, doi: 10.3390/toxins11010053.
  10. Olaleye, O., Govorukhina, N., van de Merbel, N. C., and Bischoff, R. (2021) Non-antibody-based binders for the enrichment of proteins for analysis by mass spectrometry, Biomolecules, 11, 1791, doi: 10.3390/biom11121791.
  11. Bondos, S. E., Dunker, A. K., and Uversky, V. N. (2022) Intrinsically disordered proteins play diverse roles in cell signaling, Cell Commun. Signal., 20, 20, doi: 10.1186/s12964-022-00821-7.
  12. Karlsson, O. A., Ramirez, J., Öberg, D., Malmqvist, T., Engström, Å., et al. (2015) Design of a PDZbody, a bivalent binder of the E6 protein from human papillomavirus, Sci. Rep., 5, 9382, doi: 10.1038/srep09382.
  13. Sha, F., Salzman, G., Gupta, A., and Koide, S. (2017) Monobodies and other synthetic binding proteins for expanding protein science, Protein Sci., 26, 910-924, doi: 10.1002/pro.3148.
  14. Hantschel, O., Biancalana, M., and Koide, S. (2020) Monobodies as enabling tools for structural and mechanistic biology, Curr. Opin. Struct. Biol., 60, 167-174, doi: 10.1016/j.sbi.2020.01.015.
  15. McConnell, S. J., and Hoess, R. H. (1995) Tendamistat as a scaffold for conformationally constrained phage peptide libraries, J. Mol. Biol., 250, 460-470, doi: 10.1006/jmbi.1995.0390.
  16. Ciesiołkiewicz, A., Lizandra Perez, J., and Berlicki, Ł. (2022) Miniproteins in medicinal chemistry, Bioorg. Med. Chem. Lett., 71, 128806, doi: 10.1016/j.bmcl.2022.128806.
  17. Kolmar, H. (2008) Alternative binding proteins: biological activity and therapeutic potential of cystine-knot miniproteins, FEBS J., 275, 2684-2690, doi: 10.1111/j.1742-4658.2008.06440.x.
  18. Silverman, J., Liu, Q., Bakker, A., To, W., Duguay, A., et al. (2005) Multivalent avimer proteins evolved by exon shuffling of a family of human receptor domains, Nat. Biotechnol., 23, 1556-1561, doi: 10.1038/nbt1166.
  19. Tiede, C., Tang, A. A. S., Deacon, S. E., Mandal, U., Nettleship, J. E., et al. (2014) Adhiron: a stable and versatile peptide display scaffold for molecular recognition applications, Protein Eng. Des. Sel., 27, 145-155, doi: 10.1093/protein/gzu007.
  20. Tiede, C., Bedford, R., Heseltine, S. J., Smith, G., Wijetunga, I., et al. (2017) Affimer proteins are versatile and renewable affinity reagents, Elife, 6, e24903, doi: 10.7554/eLife.24903.
  21. Shamsuddin, S. H., Jayne, D. G., Tomlinson, D. C., McPherson, M. J., and Millner, P. A. (2021) Selection and characterisation of Affimers specific for CEA recognition, Sci. Rep., 11, 744, doi: 10.1038/s41598-020-80354-6.
  22. Wicke, N., Bedford, M. R., and Howarth, M. (2021) Gastrobodies are engineered antibody mimetics resilient to pepsin and hydrochloric acid, Commun. Biol., 4, 960, doi: 10.1038/s42003-021-02487-2.
  23. Zoller, F., Markert, A., Barthe, P., Zhao, W., Weichert, W., et al. (2012) Combination of phage display and molecular grafting generates highly specific tumor-targeting miniproteins, Angew. Chem. Int. Ed. Engl., 51, 13136-13139, doi: 10.1002/anie.201203857.
  24. Cohen, I., Kayode, O., Hockla, A., Sankaran, B., Radisky, D. C., et al. (2016) Combinatorial protein engineering of proteolytically resistant mesotrypsin inhibitors as candidates for cancer therapy, Biochem. J., 473, 1329-1341, doi: 10.1042/BJ20151410.
  25. Sananes, A., Cohen, I., Shahar, A., Hockla, A., De Vita, E., et al. (2018) A potent, proteolysis-resistant inhibitor of kallikrein-related peptidase 6 (KLK6) for cancer therapy, developed by combinatorial engineering, J. Biol. Chem., 293, 12663-12680, doi: 10.1074/jbc.RA117.000871.
  26. Nishimiya, D., Kawaguchi, Y., Kodama, S., Nasu, H., Yano, H., et al. (2019) A protein scaffold, engineered SPINK2, for generation of inhibitors with high affinity and specificity against target proteases, Sci. Rep., 9, 11436, doi: 10.1038/s41598-019-47615-5.
  27. Jia, Z., Liu, Y., Ji, X., Zheng, Y., Li, Z., et al. (2021) DAKS1, a Kunitz scaffold peptide from the venom gland of Deinagkistrodon acutus prevents carotid-artery and middle-cerebral-artery thrombosis via targeting factor Xia, Pharmaceuticals (Basel), 14, 966, doi: 10.3390/ph14100966.
  28. Lee, S.-C., Park, K., Han, J., Lee, J., Kim, H. J., et al. (2012) Design of a binding scaffold based on variable lymphocyte receptors of jawless vertebrates by module engineering, Proc. Natl. Acad. Sci. USA, 109, 3299-3304, doi: 10.1073/pnas.1113193109.
  29. Hwang, D.-E., Ryou, J.-H., Oh, J. R., Han, J. W., Park, T. K., and Kim, H.-S. (2016) Anti-human VEGF repebody effectively suppresses choroidal neovascularization and vascular leakage, PLoS One, 11, e0152522, doi: 10.1371/journal.pone.0152522.
  30. Liu, H., Huang, H., Voss, C., Kaneko, T., Qin, W. T., et al. (2019) Surface loops in a single SH2 domain are capable of encoding the spectrum of specificity of the SH2 family, Mol. Cell. Proteomics, 18, 372-382, doi: 10.1074/mcp.RA118.001123.
  31. Schlatter, D., Brack, S., Banner, D. W., Batey, S., Benz, J., et al. (2012) Generation, characterization and structural data of chymase binding proteins based on the human Fyn kinase SH3 domain, MAbs, 4, 497-508, doi: 10.4161/mabs.20452.
  32. Garlich, J., Cinier, M., Chevrel, A., Perrocheau, A., Eyerman, D. J., et al. (2022) Discovery of APL-1030, a novel, high-affinity nanofitin inhibitor of C3-mediated complement activation, Biomolecules, 12, 432, doi: 10.3390/biom12030432.
  33. Gocha, T., Rao, B. M., and DasGupta, R. (2017) Identification and characterization of a novel Sso7d scaffold-based binder against Notch1, Sci. Rep., 7, 12021, doi: 10.1038/s41598-017-12246-1.
  34. Kalichuk, V., Renodon-Cornière, A., Béhar, G., Carrión, F., Obal, G., Maillasson, M., et al. (2018) A novel, smaller scaffold for Affitins: showcase with binders specific for EpCAM, Biotechnol. Bioeng., 115, 290-299, doi: 10.1002/bit.26463.
  35. Steemson, J. D., Baake, M., Rakonjac, J., Arcus, V. L., and Liddament, M. T. (2014) Tracking molecular recognition at the atomic level with a new protein scaffold based on the OB-fold, PLoS One, 9, e86050, doi: 10.1371/journal.pone.0086050.
  36. Napolitano, E. W., Villar, H. O., Kauvar, L. M., Higgins, D. L., Roberts, D., et al. (1996) Glubodies: randomized libraries of glutathione transferase enzymes, Chem. Biol., 3, 359-367, doi: 10.1016/s1074-5521(96)90119-2.
  37. Lorey, S., Fiedler, E., Kunert, A., Nerkamp, J., Lange, C., et al. (2014) Novel ubiquitin-derived high affinity binding proteins with tumor targeting properties, J. Biol. Chem., 289, 8493-8507, doi: 10.1074/jbc.M113.519884.
  38. Pham, P. N., Huličiak, M., Biedermannová, L., Černý, J., Charnavets, T., et al. (2021) Protein Binder (ProBi) as a new class of structurally robust non-antibody protein scaffold for directed evolution, Viruses, 13, 190, doi: 10.3390/v13020190.
  39. Pan, X., Thompson, M. C., Zhang, Y., Liu, L., Fraser, J. S., et al. (2020) Expanding the space of protein geometries by computational design of de novo fold families, Science, 369, 1132-1136, doi: 10.1126/science.abc0881.
  40. Desmet, J., Verstraete, K., Bloch, Y., Lorent, E., Wen, Y., et al. (2014) Structural basis of IL-23 antagonism by an Alphabody protein scaffold, Nat. Commun., 5, 5237, doi: 10.1038/ncomms6237.
  41. Koide, A., Bailey, C. W., Huang, X., and Koide, S. (1998) The fibronectin type III domain as a scaffold for novel binding proteins, J. Mol. Biol., 284, 1141-1151, doi: 10.1006/jmbi.1998.2238.
  42. Lipovsek, D. (2011) Adnectins: engineered target-binding protein therapeutics, Protein Eng. Des. Sel., 24, 3-9, doi: 10.1093/protein/gzq097.
  43. Sullivan, M. A., Brooks, L. R., Weidenborner, P., Domm, W., Mattiacio, J., et al. (2013) Anti-idiotypic monobodies derived from a fibronectin scaffold, Biochemistry, 52, 1802-1813, doi: 10.1021/bi3016668.
  44. Chandler, P. G., and Buckle, A. M. (2020) Development and differentiation in monobodies based on the fibronectin type 3 domain, Cells, 9, E610, doi: 10.3390/cells9030610.
  45. Akkapeddi, P., Teng, K. W., and Koide, S. (2021) Monobodies as tool biologics for accelerating target validation and druggable site discovery, RSC Med. Chem., 12, 1839-1853, doi: 10.1039/d1md00188d.
  46. Batori, V., Koide, A., and Koide, S. (2002) Exploring the potential of the monobody scaffold: effects of loop elongation on the stability of a fibronectin type III domain, Protein Eng., 15, 1015-1020, doi: 10.1093/protein/15.12.1015.
  47. Kükenshöner, T., Schmit, N. E., Bouda, E., Sha, F., Pojer, F., et al. (2017) Selective targeting of SH2 domain-phosphotyrosine interactions of Src family tyrosine kinases with monobodies, J. Mol. Biol., 429, 1364-1380, doi: 10.1016/j.jmb.2017.03.023.
  48. Gross, G. G., Junge, J. A., Mora, R. J., Kwon, H.-B., Olson, C. A., et al. (2013) Recombinant probes for visualizing endogenous synaptic proteins in living neurons, Neuron, 78, 971-985, doi: 10.1016/j.neuron.2013.04.017.
  49. Porebski, B. T., Conroy, P. J., Drinkwater, N., Schofield, P., Vazquez-Lombardi, R., et al. (2016) Circumventing the stability-function trade-off in an engineered FN3 domain, Protein Eng. Des. Sel., 29, 541-550, doi: 10.1093/protein/gzw046.
  50. Porebski, B. T., Nickson, A. A., Hoke, D. E., Hunter, M. R., Zhu, L., et al. (2015) Structural and dynamic properties that govern the stability of an engineered fibronectin type III domain, Protein Eng. Des. Sel., 28, 67-78, doi: 10.1093/protein/gzv002.
  51. Chandler, P. G., Tan, L. L., Porebski, B. T., Green, J. S., Riley, B. T., et al. (2021) Mutational and biophysical robustness in a prestabilized monobody, J. Biol. Chem., 296, 100447, doi: 10.1016/j.jbc.2021.100447.
  52. Deuschle, F.-C., Ilyukhina, E., and Skerra, A. (2021) Anticalin® proteins: from bench to bedside, Expert Opin. Biol. Ther., 21, 509-518, doi: 10.1080/14712598.2021.1839046.
  53. Achatz, S., Jarasch, A., and Skerra, A. (2022) Structural plasticity in the loop region of engineered lipocalins with novel ligand specificities, so-called Anticalins, J. Struct. Biol., 6, 100054, doi: 10.1016/j.yjsbx.2021.100054.
  54. Gebauer, M., Schiefner, A., Matschiner, G., and Skerra, A. (2013) Combinatorial design of an anticalin directed against the extra-domain B for the specific targeting of oncofetal fibronectin, J. Mol. Biol., 425, 780-802, doi: 10.1016/j.jmb.2012.12.004.
  55. Chi, Y., Remsik, J., Kiseliovas, V., Derderian, C., Sener, U., et al. (2020) Cancer cells deploy lipocalin-2 to collect limiting iron in leptomeningeal metastasis, Science, 369, 276-282, doi: 10.1126/science.aaz2193.
  56. Yang, J., Bielenberg, D. R., Rodig, S. J., Doiron, R., Clifton, M. C., et al. (2009) Lipocalin 2 promotes breast cancer progression, Proc. Natl. Acad. Sci. USA, 106, 3913-3918, doi: 10.1073/pnas.0810617106.
  57. Chakraborty, S., Kaur, S., Guha, S., and Batra, S. K. (2012) The multifaceted roles of neutrophil gelatinase associated lipocalin (NGAL) in inflammation and cancer, Biochim. Biophys. Acta, 1826, 129-169, doi: 10.1016/j.bbcan.2012.03.008.
  58. Crescenzi, E., Leonardi, A., and Pacifico, F. (2021) NGAL as a potential target in tumor microenvironment, Int. J. Mol. Sci., 22, 12333, doi: 10.3390/ijms222212333.
  59. Xu, B., Zheng, W., Jin, D., Wang, D., Liu, X., and Qin, X. (2012) Treatment of pancreatic cancer using an oncolytic virus harboring the lipocalin-2 gene, Cancer, 118, 5217-5226, doi: 10.1002/cncr.27535.
  60. Xu, B., Zheng, W.-Y., Feng, J.-F., Huang, X.-Y., and Ge, H. (2013) One potential oncolytic adenovirus expressing Lipocalin-2 for colorectal cancer therapy, Cancer Biother. Radiopharm., 28, 415-422, doi: 10.1089/cbr.2012.1352.
  61. Nishimura, S., Yamamoto, Y., Sugimoto, A., Kushiyama, S., Togano, S., et al. (2022) Lipocalin-2 negatively regulates epithelial-mesenchymal transition through matrix metalloprotease-2 downregulation in gastric cancer, Gastric Cancer, 25, 850-861, doi: 10.1007/s10120-022-01305-w.
  62. Pinyopornpanish, K., Phrommintikul, A., Angkurawaranon, C., Kumfu, S., Angkurawaranon, S., et al. (2022) Circulating Lipocalin-2 level is positively associated with cognitive impairment in patients with metabolic syndrome, Sci. Rep., 12, 4635, doi: 10.1038/s41598-022-08286-x.
  63. Friedman, M., Lindström, S., Ekerljung, L., Andersson-Svahn, H., Carlsson, J., et al. (2009) Engineering and characterization of a bispecific HER2 x EGFR-binding affibody molecule, Biotechnol. Appl. Biochem., 54, 121-131, doi: 10.1042/BA20090096.
  64. Gorman, K., McGinnis, J., and Kay, B. (2018) Generating FN3-based affinity reagents through phage display, Curr. Protoc. Chem. Biol., 10, e39, doi: 10.1002/cpch.39.
  65. Давыдова Е. К. (2022) Белковая инженерия: достижения фагового дисплея в науке и медицине, Усп. Биол. Хим., 62, 319.
  66. Zhang, Y., Thangam, R., You, S.-H., Sultonova, R. D., Venu, A., et al. (2021) Engineering calreticulin-targeting monobodies to detect immunogenic cell death in cancer chemotherapy, Cancers (Basel), 13, 2801, doi: 10.3390/cancers13112801.
  67. Cetin, M., Evenson, W. E., Gross, G. G., Jalali-Yazdi, F., Krieger, D., et al. (2017) RasIns: genetically encoded intrabodies of activated Ras proteins, J. Mol. Biol., 429, 562-573, doi: 10.1016/j.jmb.2016.11.008.
  68. Olson, C. A., and Roberts, R. W. (2007) Design, expression, and stability of a diverse protein library based on the human fibronectin type III domain, Protein Sci., 16, 476-484, doi: 10.1110/ps.062498407
  69. Храмцов Ю. В., Уласов А. В., Лупанова Т. Н., Георгиев Г. П., Соболев А. С. (2022) Доставка антителоподобных молекул, монободи, способных связываться с нуклеокапсидным белком вируса SARS-COV-2, в клетки-мишени, Докл. РАН. Науки Жизни, 506, 68, doi: 10.31857/S2686738922050146.
  70. Lipovsek, D., Lippow, S. M., Hackel, B. J., Gregson, M. W., Cheng, P., et al. (2007) Evolution of an interloop disulfide bond in high-affinity antibody mimics based on fibronectin type III domain and selected by yeast surface display: molecular convergence with single-domain camelid and shark antibodies, J. Mol. Biol., 368, 1024-1041, doi: 10.1016/j.jmb.2007.02.029.
  71. Riihimäki, T. A., Hiltunen, S., Rangl, M., Nordlund, H. R., Määttä, J. A. E., et al. (2011) Modification of the loops in the ligand-binding site turns avidin into a steroid-binding protein, BMC Biotechnol., 11, 64, doi: 10.1186/1472-6750-11-64.
  72. Hytönen, V. P. (2020) (Strept)avidin as a template for ligands other than biotin: An overview, Methods Enzymol., 633, 21-28, doi: 10.1016/bs.mie.2019.10.029.
  73. Kiss, C., Fisher, H., Pesavento, E., Dai, M., Valero, R., et al. (2006) Antibody binding loop insertions as diversity elements, Nucleic Acids Res., 34, e132, doi: 10.1093/nar/gkl681.
  74. Kadonosono, T., Yabe, E., Furuta, T., Yamano, A., Tsubaki, T., et al. (2014) A fluorescent protein scaffold for presenting structurally constrained peptides provides an effective screening system to identify high affinity target-binding peptides, PLoS One, 9, e103397, doi: 10.1371/journal.pone.0103397.
  75. Chee, S. M. Q., Wongsantichon, J., Yi, L. S., Sana, B., Frosi, Y., et al. (2021) Functional display of bioactive peptides on the vGFP scaffold, Sci. Rep., 11, 10127, doi: 10.1038/s41598-021-89421-y.
  76. Rinne, S. S., Yin, W., Borras, A. M., Abouzayed, A., Leitao, C. D., et al. (2022) Targeting tumor cells overexpressing the human epidermal growth factor receptor 3 with potent drug conjugates based on affibody molecules, Biomedicines, 10, 1293, doi: 10.3390/biomedicines10061293.
  77. Sokolova, E., Kutova, O., Grishina, A., Pospelov, A., Guryev, E., et al. (2019) Penetration efficiency of antitumor agents in ovarian cancer spheroids: the case of recombinant targeted toxin DARPin-LoPE and the chemotherapy drug, doxorubicin, Pharmaceutics, 11, 219, doi: 10.3390/pharmaceutics11050219.
  78. Sachdev, S., Cabalteja, C. C., and Cheloha, R. W. (2021) Strategies for targeting cell surface proteins using multivalent conjugates and chemical biology, Methods Cell Biol., 166, 205-222, doi: 10.1016/bs.mcb.2021.06.004.
  79. Шипунова В. О., Деев С. М. (2022) Распознающие cкаффолдовые полипептиды как инструмент для адресной доставки наноструктур in vitro и in vivo, Acta Naturae, 14, 54, doi: 10.32607/actanaturae.11545.
  80. Deyev, S., Proshkina, G., Baryshnikova, O., Ryabova, A., Avishai, G., et al. (2018) Selective staining and eradication of cancer cells by protein-carrying DARPin-functionalized liposomes, Eur. J. Pharm. Biopharm., 130, 296-305, doi: 10.1016/j.ejpb.2018.06.026.
  81. Nazari, M., Emamzadeh, R., Jahanpanah, M., Yazdani, E., and Radmanesh, R. (2022) A recombinant affitoxin derived from a HER3 affibody and diphteria-toxin has potent and selective antitumor activity, Int. J. Biol. Macromol., 219, 1122-1134, doi: 10.1016/j.ijbiomac.2022.08.150.
  82. Lipovšek, D., Carvajal, I., Allentoff, A. J., Barros, A., Brailsford, J., et al. (2018) Adnectin-drug conjugates for Glypican-3-specific delivery of a cytotoxic payload to tumors, Protein Eng. Des. Sel., 31, 159-171, doi: 10.1093/protein/gzy013.
  83. Karsten, L., Janson, N., Le Joncour, V., Alam, S., Müller, B., et al. (2022) Bivalent EGFR-targeting DARPin-MMAE conjugates, Int. J. Mol. Sci., 23, 2468, doi: 10.3390/ijms23052468.
  84. Sharma, R., Suman, S. K., and Mukherjee, A. (2022) Antibody-based radiopharmaceuticals as theranostic agents: an overview, Curr. Med. Chem., 29, 5979, doi: 10.2174/0929867329666220607160559.
  85. Luo, R., Liu, H., and Cheng, Z. (2022) Protein scaffolds: antibody alternatives for cancer diagnosis and therapy, RSC Chem. Biol., 3, 830-847, doi: 10.1039/d2cb00094f.
  86. Klont, F., Hadderingh, M., Horvatovich, P., Ten Hacken, N. H. T., and Bischoff, R. (2018) Affimers as an alternative to antibodies in an affinity LC-MS assay for quantification of the soluble receptor of advanced glycation end-products (sRAGE) in human serum, J. Proteome Res., 17, 2892-2899, doi: 10.1021/acs.jproteome.8b00414.
  87. Mayoral-Peña, K., González Peña, O. I., Orrantia Clark, A. M., Flores-Vallejo, R. D. C., Oza, G., et al. (2022) Biorecognition engineering technologies for cancer diagnosis: a systematic literature review of non-conventional and plausible sensor development methods, Cancers (Basel), 14, 1867, doi: 10.3390/cancers14081867.
  88. Шилова О. Н., Деев С. М. (2019) Дарпины - перспективные адресные белки для тераностики, Acta Naturae, 11, 42, doi: 10.32607/20758251-2019-11-4-42-53.
  89. Shipunova, V. O., Kolesnikova, O. A., Kotelnikova, P. A., Soloviev, V. D., Popov, A. A., et al. (2021) Comparative evaluation of engineered polypeptide scaffolds in HER2-targeting magnetic nanocarrier delivery, ACS Omega, 6, 16000, doi: 10.1021/acsomega.1c01811.
  90. Mamluk, R., Carvajal, I. M., Morse, B. A., Wong, H., Abramowitz, J., et al. (2010) Anti-tumor effect of CT-322 as an adnectin inhibitor of vascular endothelial growth factor receptor-2, MAbs, 2, 199-208, doi: 10.4161/mabs.2.2.11304.
  91. Tolmachev, V., and Orlova, A. (2020) Affibody molecules as targeting vectors for PET imaging, Cancers (Basel), 12, E651, doi: 10.3390/cancers12030651.
  92. Deyev, S., Vorobyeva, A., Schulga, A., Proshkina, G., Güler, R., et al. (2019) Comparative evaluation of two DARPin variants: effect of affinity, size, and label on tumor targeting properties, Mol. Pharm., 16, 995-1008, doi: 10.1021/acs.molpharmaceut.8b00922.
  93. Wang, Y., Ballou, B., Schmidt, B. F., Andreko, S., St Croix, C. M., et al. (2017) Affibody-targeted fluorogen activating protein for in vivo tumor imaging, Chem. Commun. (Camb.), 53, 2001, doi: 10.1039/c6cc09137g.
  94. Yun, M., Kim, D.-Y., Lee, J.-J., Kim, H.-S., Kim, H.-S., et al. (2017) A high-affinity repebody for molecular imaging of EGFR-expressing malignant tumors, Theranostics, 7, 2620-2633, doi: 10.7150/thno.18096.
  95. Mączyńska, J., Raes, F., Da Pieve, C., Turnock, S., Boult, J. K. R., et al. (2022) Triggering anti-GBM immune response with EGFR-mediated photoimmunotherapy, BMC Med., 20, 16, doi: 10.1186/s12916-021-02213-z.
  96. Lui, B. G., Salomon, N., Wüstehube-Lausch, J., Daneschdar, M., Schmoldt, H.-U., et al. (2020) Targeting the tumor vasculature with engineered cystine-knot miniproteins, Nat. Commun., 11, 295, doi: 10.1038/s41467-019-13948-y.
  97. Балалаева И. В., Крылова Л. В., Карпова М. А., Шульга А. А., Коновалова Е. В. (2023) Синергический эффект комбинированного действия таргетной и фотодинамической терапии в отношении HER2-положительного рака молочной железы, Докл. РАН. Науки Жизни, 508, 48, doi: 10.31857/S268673892270007X.
  98. Proshkina, G. M., Shramova, E. I., Shilova, M. V., Zelepukin, I. V., Shipunova, V. O., et al. (2021) DARPin_9-29-targeted gold nanorods selectively suppress HER2-positive tumor growth in mice, Cancers (Basel), 13, 5235, doi: 10.3390/cancers1320523.
  99. Shramova, E., Proshkina, G., Shipunova, V., Ryabova, A., Kamyshinsky, R., et al. (2020) Dual targeting of cancer cells with DARPin-based toxins for overcoming tumor escape, Cancers (Basel), 12, E3014, doi: 10.3390/cancers12103014.
  100. Eijkenboom, L., Palacio-Castañeda, V., Groenman, F., Braat, D., Beerendonk, C., et al. (2021) Assessing the use of tumor-specific DARPin-toxin fusion proteins for ex vivo purging of cancer metastases from human ovarian cortex before autotransplantation, F. S. Sci., 2, 330-344, doi: 10.1016/j.xfss.2021.09.004.
  101. Xu, T., Schulga, A., Konovalova, E., Rinne, S. S., Zhang, H., et al. (2023) Feasibility of co-targeting HER3 and EpCAM using seribantumab and DARPin-toxin fusion in a pancreatic cancer xenograft model, Int. J. Mol. Sci., 24, 2838, doi: 10.3390/ijms24032838.
  102. Hanauer, J. R. H., Koch, V., Lauer, U. M., and Mühlebach, M. D. (2019) High-affinity DARPin allows targeting of MeV to glioblastoma multiforme in combination with protease targeting without loss of potency, Mol. Ther. Oncolytics, 15, 186-200, doi: 10.1016/j.omto.2019.10.004.
  103. Lal, S., and Raffel, C. (2017) Using cystine knot proteins as a novel approach to retarget oncolytic measles virus, Mol. Ther. Oncolytics, 7, 57-66, doi: 10.1016/j.omto.2017.09.005.
  104. Strecker, M. I., Wlotzka, K., Strassheimer, F., Roller, B., Ludmirski, G., et al. (2022) AAV-mediated gene transfer of a checkpoint inhibitor in combination with HER2-targeted CAR-NK cells as experimental therapy for glioblastoma, Oncoimmunology, 11, 2127508, doi: 10.1080/2162402X.2022.2127508.
  105. Zajc, C. U., Salzer, B., Taft, J. M., Reddy, S. T., Lehner, M., and Traxlmayr, M. W. (2021) Driving CARs with alternative navigation tools - the potential of engineered binding scaffolds, FEBS J., 288, 2103-2118, doi: 10.1111/febs.15523.
  106. Stepanov, A. V., Kalinin, R. S., Shipunova, V. O., Zhang, D., Xie, J., et al. (2022) Switchable targeting of solid tumors by BsCAR T cells, Proc. Natl. Acad. Sci. USA, 119, e2210562119, doi: 10.1073/pnas.2210562119.
  107. Parfenyev, S., Singh, A., Fedorova, O., Daks, A., Kulshreshtha, R., and Barlev, N. A. (2021) Interplay between p53 and non-coding RNAs in the regulation of EMT in breast cancer, Cell Death Dis., 12, 17, doi: 10.1038/s41419-020-03327-7.
  108. Lezina, L., Aksenova, V., Fedorova, O., Malikova, D., Shuvalov, O., Antonov, A. V., et al. (2015) KMT Set7/9 affects genotoxic stress response via the Mdm2 axis, Oncotarget, 6, 25843-25855, doi: 10.18632/oncotarget.4584.
  109. Davidovich, P., Aksenova, V., Petrova, V., Tentler, D., Orlova, D., et al. (2015) Discovery of novel isatin-based p53 inducers, ACS Med. Chem. Lett., 6, 856-860, doi: 10.1021/acsmedchemlett.5b00011.
  110. Bulatov, E., Sayarova, R., Mingaleeva, R., Miftakhova, R., Gomzikova, M., et al. (2018) Isatin-Schiff base-copper (II) complex induces cell death in p53-positive tumors, Cell Death Discov., 4, 103, doi: 10.1038/s41420-018-0120-z.
  111. Lau, S.-Y., Siau, J. W., Sobota, R. M., Wang, C.-I., Zhong, P., et al. (2018) Synthetic 10FN3-based mono- and bivalent inhibitors of MDM2/X function, Protein Eng. Des. Sel., 31, 301-312, doi: 10.1093/protein/gzy018.
  112. Spencer-Smith, R., Koide, A., Zhou, Y., Eguchi, R. R., Sha, F., et al. (2017) Inhibition of RAS function through targeting an allosteric regulatory site, Nat. Chem. Biol., 13, 62-68, doi: 10.1038/nchembio.2231.
  113. Teng, K. W., Tsai, S. T., Hattori, T., Fedele, C., Koide, A., et al. (2021) Selective and noncovalent targeting of RAS mutants for inhibition and degradation, Nat. Commun., 12, 2656, doi: 10.1038/s41467-021-22969-5.
  114. Khan, I., Koide, A., Zuberi, M., Ketavarapu, G., Denbaum, E., et al. (2022) Identification of the nucleotide-free state as a therapeutic vulnerability for inhibition of selected oncogenic RAS mutants, Cell Rep., 38, 110322, doi: 10.1016/j.celrep.2022.110322.
  115. Wallon, L., Khan, I., Teng, K. W., Koide, A., Zuberi, M., et al. (2022) Inhibition of RAS-driven signaling and tumorigenesis with a pan-RAS monobody targeting the Switch I/II pocket, Proc. Natl. Acad. Sci. USA, 119, e2204481119, doi: 10.1073/pnas.2204481119.
  116. Guillard, S., Kolasinska-Zwierz, P., Debreczeni, J., Breed, J., Zhang, J., et al. (2017) Structural and functional characterization of a DARPin which inhibits Ras nucleotide exchange, Nat. Commun., 8, 16111, doi: 10.1038/ncomms16111.
  117. Bery, N., Legg, S., Debreczeni, J., Breed, J., Embrey, K., et al. (2019) KRAS-specific inhibition using a DARPin binding to a site in the allosteric lobe, Nat. Commun., 10, 2607, doi: 10.1038/s41467-019-10419-2.
  118. McGee, J. H., Shim, S. Y., Lee, S.-J., Swanson, P. K., Jiang, S. Y., et al. (2018) Exceptionally high-affinity Ras binders that remodel its effector domain, J. Biol. Chem., 293, 3265-3280, doi: 10.1074/jbc.M117.816348.
  119. Jung, Y. H., Choi, Y., Seo, H.-D., Seo, M.-H., and Kim, H.-S. (2023) A conformation-selective protein binder for a KRAS mutant inhibits the interaction between RAS and RAF, Biochem. Biophys. Res. Commun., 645, 110-117, doi: 10.1016/j.bbrc.2023.01.019.
  120. Schmit, N. E., Neopane, K., and Hantschel, O. (2019) Targeted protein degradation through cytosolic delivery of monobody binders using bacterial toxins, ACS Chem. Biol., 14, 916-924, doi: 10.1021/acschembio.9b00113.
  121. Röth, S., Macartney, T. J., Konopacka, A., Chan, K.-H., Zhou, H., et al. (2020) Targeting endogenous K-RAS for degradation through the affinity-directed protein missile system, Cell. Chem. Biol., 27, 1151-1163.e6, doi: 10.1016/j.chembiol.2020.06.012.
  122. Kim, J. W., Cochran, F. V., and Cochran, J. R. (2015) A chemically cross-linked knottin dimer binds integrins with picomolar affinity and inhibits tumor cell migration and proliferation, J. Am. Chem. Soc., 137, 6-9, doi: 10.1021/ja508416e.
  123. Gad, S., and Ayakar, S. (2021) Protein scaffolds: A tool for multi-enzyme assembly, Biotechnol. Rep. (Amst.), 32, e00670, doi: 10.1016/j.btre.2021.e00670.
  124. Islam, M., Kehoe, H. P., Lissoos, J. B., Huang, M., Ghadban, C. E., et al. (2021) Chemical diversification of simple synthetic antibodies, ACS Chem. Biol., 16, 344-359, doi: 10.1021/acschembio.0c00865.
  125. Rabe von Pappenheim, F., Wensien, M., Ye, J., Uranga, J., Irisarri, I., et al. (2022) Widespread occurrence of covalent lysine-cysteine redox switches in proteins, Nat. Chem. Biol., 18, 368-375, doi: 10.1038/s41589-021-00966-5.
  126. Maggi, M., Pessino, G., Guardamagna, I., Lonati, L., Pulimeno, C., and Scotti, C. (2021) A targeted catalytic nanobody (T-CAN) with asparaginolytic activity, Cancers (Basel), 13, 5637, doi: 10.3390/cancers13225637.
  127. Fellouse, F. A., Barthelemy, P. A., Kelley, R. F., and Sidhu, S. S. (2006) Tyrosine plays a dominant functional role in the paratope of a synthetic antibody derived from a four amino acid code, J. Mol. Biol., 357, 100-114, doi: 10.1016/j.jmb.2005.11.092.
  128. Birtalan, S., Zhang, Y., Fellouse, F. A., Shao, L., Schaefer, G., and Sidhu, S. S. (2008) The intrinsic contributions of tyrosine, serine, glycine and arginine to the affinity and specificity of antibodies, J. Mol. Biol., 377, 1518-1528, doi: 10.1016/j.jmb.2008.01.093.
  129. Gilbreth, R. N., Esaki, K., Koide, A., Sidhu, S. S., and Koide, S. (2008) A dominant conformational role for amino acid diversity in minimalist protein-protein interfaces, J. Mol. Biol., 381, 407-418, doi: 10.1016/j.jmb.2008.06.014.
  130. Bonvin, P., Venet, S., Fontaine, G., Ravn, U., Gueneau, F., Kosco-Vilbois, M., et al. (2015) De novo isolation of antibodies with pH-dependent binding properties, MAbs, 7, 294-302, doi: 10.1080/19420862.2015.1006993.
  131. Hackel, B. J., and Wittrup, K. D. (2010) The full amino acid repertoire is superior to serine/tyrosine for selection of high affinity immunoglobulin G binders from the fibronectin scaffold, Protein Eng. Des. Sel., 23, 211-219, doi: 10.1093/protein/gzp083.
  132. Svilenov, H. L., Sacherl, J., Protzer, U., Zacharias, M., and Buchner, J. (2021) Mechanistic principles of an ultra-long bovine CDR reveal strategies for antibody design, Nat. Commun., 12, 6737, doi: 10.1038/s41467-021-27103-z.
  133. Schilling, J., Schöppe, J., and Plückthun, A. (2014) From DARPins to LoopDARPins: novel LoopDARPin design allows the selection of low picomolar binders in a single round of ribosome display, J. Mol. Biol., 426, 691-721, doi: 10.1016/j.jmb.2013.10.026.

Copyright (c) 2023 Russian Academy of Sciences

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies