Engineered platelets as targeted protein degraders and application to breast cancer models – Nature Biotechnology

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  • Sakamoto, K. M. et al. PROTACs: chimeric molecules that target proteins to the Skp1–Cullin-F box complex for ubiquitination and degradation. Proc. Natl Acad. Sci. USA 98, 8554–8559 (2001).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Banik, S. M. et al. Lysosome-targeting chimaeras for degradation of extracellular proteins. Nature 584, 291–297 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Pance, K. et al. Modular cytokine receptor-targeting chimeras for targeted degradation of cell surface and extracellular proteins. Nat. Biotechnol. 41, 273–281 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Alabi, S. B. & Crews, C. M. Major advances in targeted protein degradation: PROTACs, LYTACs, and MADTACs. J. Biol. Chem. 296, 100647 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Bekes, M., Langley, D. R. & Crews, C. M. PROTAC targeted protein degraders: the past is prologue. Nat. Rev. Drug Discov. 21, 181–200 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Chen, Y. et al. Small-molecule ferritin degrader as a pyroptosis inducer. J. Am. Chem. Soc. 145, 9815–9824 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Wei, J. et al. Harnessing the E3 ligase KEAP1 for targeted protein degradation. J. Am. Chem. Soc. 143, 15073–15083 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Imaide, S. et al. Trivalent PROTACs enhance protein degradation via combined avidity and cooperativity. Nat. Chem. Biol. 17, 1157–1167 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Caianiello, D. F. et al. Bifunctional small molecules that mediate the degradation of extracellular proteins. Nat. Chem. Biol. 17, 947–953 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Ahn, G. et al. LYTACs that engage the asialoglycoprotein receptor for targeted protein degradation. Nat. Chem. Biol. 17, 937–946 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Guedeney, N., Cornu, M., Schwalen, F., Kieffer, C. & Voisin-Chiret, A. S. PROTAC technology: a new drug design for chemical biology with many challenges in drug discovery. Drug Discov. Today 28, 103395 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Chen, Y. et al. Proteolysis-targeting chimera (PROTAC) delivery system: advancing protein degraders towards clinical translation. Chem. Soc. Rev. 51, 5330–5350 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Garber, K. The PROTAC gold rush. Nat. Biotechnol. 40, 12–16 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Ahn, G. et al. Elucidating the cellular determinants of targeted membrane protein degradation by lysosome-targeting chimeras. Science 382, eadf6249 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Gadd, M. S. et al. Structural basis of PROTAC cooperative recognition for selective protein degradation. Nat. Chem. Biol. 13, 514–521 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Takahashi, D. et al. AUTACs: cargo-specific degraders using selective autophagy. Mol. Cell 76, 797–810.e10 (2019).

  • Li, Z. et al. Allele-selective lowering of mutant HTT protein by HTT–LC3 linker compounds. Nature 575, 203–209 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Stanton, B. Z., Chory, E. J. & Crabtree, G. R. Chemically induced proximity in biology and medicine. Science 359, eaao5902 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Bai, L. et al. A potent and selective small-molecule degrader of STAT3 achieves complete tumor regression in vivo. Cancer Cell 36, 498–511.e17 (2019).

  • Chirnomas, D., Hornberger, K. R. & Crews, C. M. Protein degraders enter the clinic—a new approach to cancer therapy. Nat. Rev. Clin. Oncol. 20, 265–278 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Wurz, R. P. et al. Affinity and cooperativity modulate ternary complex formation to drive targeted protein degradation. Nat. Commun. 14, 4177 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Tamura, T. et al. Rapid labelling and covalent inhibition of intracellular native proteins using ligand-directed N-acyl-N-alkyl sulfonamide. Nat. Commun. 9, 1870 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Beerkens, B. L. H. et al. N-Acyl-N-alkyl sulfonamide probes for ligand-directed covalent labeling of GPCRs: the adenosine A2B receptor as case study. ACS Chem. Biol. 19, 1554–1562 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Kawano, M. et al. Lysine-reactive N-acyl-N-aryl sulfonamide warheads: improved reaction properties and application in the covalent inhibition of an ibrutinib-resistant BTK mutant. J. Am. Chem. Soc. 145, 26202–26212 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Caldas-Lopes, E. et al. Hsp90 inhibitor PU-H71, a multimodal inhibitor of malignancy, induces complete responses in triple-negative breast cancer models. Proc. Natl Acad. Sci. USA 106, 8368–8373 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Schopf, F. H., Biebl, M. M. & Buchner, J. The HSP90 chaperone machinery. Nat. Rev. Mol. Cell Biol. 18, 345–360 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Cuesta, A., Wan, X., Burlingame, A. L. & Taunton, J. Ligand conformational bias drives enantioselective modification of a surface-exposed lysine on HSP90. J. Am. Chem. Soc. 142, 3392–3400 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Filippakopoulos, P. et al. Selective inhibition of BET bromodomains. Nature 468, 1067–1073 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Zhou, X. et al. Therapeutic targeting of BET bromodomain protein, BRD4, delays cyst growth in ADPKD. Hum. Mol. Genet. 24, 3982–3993 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Bondeson, D. P. et al. Catalytic in vivo protein knockdown by small-molecule PROTACs. Nat. Chem. Biol. 11, 611–617 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wang, C. et al. In situ activation of platelets with checkpoint inhibitors for post-surgical cancer immunotherapy. Nat. Biomed. Eng. 1, 0011 (2017).

  • Hu, Q. et al. Inhibition of post-surgery tumour recurrence via a hydrogel releasing CAR-T cells and anti-PDL1-conjugated platelets. Nat. Biomed. Eng. 5, 1038–1047 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wang, Y. et al. Active recruitment of anti-PD-1-conjugated platelets through tumor-selective thrombosis for enhanced anticancer immunotherapy. Sci. Adv. 9, eadf6854 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Michael, J. V. et al. Platelet microparticles infiltrating solid tumors transfer miRNAs that suppress tumor growth. Blood 130, 567–580 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Zengerle, M., Chan, K. H. & Ciulli, A. Selective small molecule induced degradation of the BET bromodomain protein BRD4. ACS Chem. Biol. 10, 1770–1777 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Hu, J. et al. Precise conformational control yielding highly potent and exceptionally selective BRD4 degraders with strong antitumor activity. J. Med. Chem. 66, 8222–8237 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Jia, H. et al. Immunotherapy for triple-negative breast cancer: existing challenges and exciting prospects. Drug Resist. Updat. 32, 1–15 (2017).

    Article 
    PubMed 

    Google Scholar 

  • Gangi, A. et al. Breast-conserving therapy for triple-negative breast cancer. JAMA Surg. 149, 252–258 (2014).

    Article 
    PubMed 

    Google Scholar 

  • Trepel, J., Mollapour, M., Giaccone, G. & Neckers, L. Targeting the dynamic HSP90 complex in cancer. Nat. Rev. Cancer 10, 537–549 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wang, X. et al. The regulatory mechanism of HSP90α secretion and its function in tumor malignancy. Proc. Natl Acad. Sci. USA 106, 21288–21293 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Li, W. et al. Extracellular HSP90 (eHSP90) as the actual target in clinical trials: intentionally or unintentionally. Int. Rev. Cell Mol. Biol. 303, 203–235 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Murshid, A., Gong, J., Stevenson, M. A. & Calderwood, S. K. Heat shock proteins and cancer vaccines: developments in the past decade and chaperoning in the decade to come. Expert Rev. Vaccines 10, 1553–1568 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Hance, M. W. et al. Secreted HSP90 is a novel regulator of the epithelial to mesenchymal transition (EMT) in prostate cancer. J. Biol. Chem. 287, 37732–37744 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Cheng, C. F. et al. Transforming growth factor α (TGFα)-stimulated secretion of HSP90α: using the receptor LRP-1/CD91 to promote human skin cell migration against a TGFβ-rich environment during wound healing. Mol. Cell. Biol. 28, 3344–3358 (2008).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Loppinet, E. et al. Targeted lysosomal degradation of secreted and cell surface proteins through the LRP-1 pathway. J. Am. Chem. Soc. 145, 18705–18710 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Prasad, J. M., Migliorini, M., Galisteo, R. & Strickland, D. K. Generation of a potent low density lipoprotein receptor-related protein 1 (LRP1) antagonist by engineering a stable form of the receptor-associated protein (RAP) D3 domain. J. Biol. Chem. 290, 17262–17268 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Secli, L., Fusella, F., Avalle, L. & Brancaccio, M. The dark-side of the outside: how extracellular heat shock proteins promote cancer. Cell. Mol. Life Sci. 78, 4069–4083 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Li, C. W. et al. Eradication of triple-negative breast cancer cells by targeting glycosylated PD-L1. Cancer Cell 33, 187–201.e10 (2018).

  • Patel, S. R., Hartwig, J. H. & Italiano, J. E. Jr. The biogenesis of platelets from megakaryocyte proplatelets. J. Clin. Invest. 115, 3348–3354 (2005).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Garcia, B. A. et al. The platelet microparticle proteome. J. Proteome Res. 4, 1516–1521 (2005).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Hu, C. M. et al. Nanoparticle biointerfacing by platelet membrane cloaking. Nature 526, 118–121 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Fang, R. H., Gao, W. & Zhang, L. Targeting drugs to tumours using cell membrane-coated nanoparticles. Nat. Rev. Clin. Oncol. 20, 33–48 (2023).

    Article 
    PubMed 

    Google Scholar 

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