Adenoviral vector with shield and adapter increases tumor specificity and escapes liver and immune control

Nature Communications

Volumn 9, Issue 1, 2018, Pages

  Schmid, Markus ^a   Ernst, Patrick ^a   Honegger, Annemarie ^a   Suomalainen, Maarit ^a   Zimmermann, Martina ^a   Braun, Lukas ^b   Stauffer, Sarah ^a   Thom, Cristian ^a   Dreier, Birgit ^a   Eibauer, Matthias ^a   Kipar, Anja ^a   Vogel, Viola ^b   Greber, Urs F ^a   Medalia, Ohad ^a,c   Plückthun, Andreas ^a  

^a UNIVERSITY OF ZURICH   (Switzerland)

^b ETH ZURICH   (Switzerland)

^c BEN GURION UNIVERSITY OF THE NEGEV   (Israel)

Author keywords

[No Author keywords available]

Indexed keywords

ADAPTOR PROTEIN; ADENOVIRUS VECTOR; COAT PROTEIN; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR 2; SINGLE CHAIN FRAGMENT VARIABLE ANTIBODY; CAPSID PROTEIN; EGFR PROTEIN, HUMAN; ERBB2 PROTEIN, HUMAN; HEXON CAPSID PROTEIN, ADENOVIRUS;

CANCER; CELL; CRYSTALLOGRAPHY; ELECTRON MICROSCOPY; GENE; PROTEIN; TUMOR; VIRUS; VIRUS PARTICLE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CANCER CELL; CONTROLLED STUDY; CRYSTALLOGRAPHY; ELECTRON MICROSCOPY; GENE; GENE THERAPY; HUMAN; HUMAN ADENOVIRUS 5; HUMAN CELL; HUMAN TISSUE; IN VIVO STUDY; LIVER; MOUSE; NONHUMAN; PROTEIN ENGINEERING; TRANSGENE; VIRAL GENE DELIVERY SYSTEM; VIRION; ADMINISTRATION AND DOSAGE; ANIMAL; CHEMISTRY; DRUG SCREENING; FEMALE; GENE TRANSFER; GENE VECTOR; GENETICS; HUMAN ADENOVIRUS C; IMMUNOLOGY; METABOLISM; MOLECULARLY TARGETED THERAPY; PATHOGENICITY; PHYSIOLOGY; PROCEDURES; SPLEEN; TRANSGENIC MOUSE; TUMOR CELL LINE; VIROLOGY; X RAY CRYSTALLOGRAPHY;

HUMAN ADENOVIRUS TYPE 5;

ADENOVIRUSES, HUMAN; ANIMALS; CAPSID PROTEINS; CELL LINE, TUMOR; CRYSTALLOGRAPHY, X-RAY; FEMALE; GENE TRANSFER TECHNIQUES; GENETIC VECTORS; HUMANS; LIVER; MICE, TRANSGENIC; MOLECULAR TARGETED THERAPY; RECEPTOR, EPIDERMAL GROWTH FACTOR; RECEPTOR, ERBB-2; SINGLE-CHAIN ANTIBODIES; SPLEEN; VIRION; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 85041354061     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/s41467-017-02707-6     Document Type: Article

References (69)

1. Naldini, L. Gene therapy returns to centre stage. Nature 526, 351-360 (2015).
2. Scott, L. J. Alipogene tiparvovec: a review of its use in adults with familial lipoprotein lipase deficiency. Drugs 75, 175-182 (2015).
3. Ginn, S. L. et al. Gene therapy clinical trials worldwide to 2012-an update. J. Gene. Med. 15, 65-77 (2013).
4. Abedi, M. R. The Journal of Gene Medicine-Wiley Online Library. Gene therapy trials worldwide. http://www.abedia.com/wiley/vectors.php (accessed on: 06/10/2017).
5. Hendrickx, R. et al. Innate immunity to adenovirus. Hum. Gene. Ther. 25, 265-284 (2014).
6. Kasala, D. et al. Utilizing adenovirus vectors for gene delivery in cancer. Expert Opin. Drug. Deliv. 11, 379-392 (2014).
7. Kallel, H. & Kamen, A. A. Large-scale adenovirus and poxvirus-vectored vaccine manufacturing to enable clinical trials. Biotechnol. J. 10, 741-747 (2015).
8. Escors, D. & Breckpot, K. Lentiviral vectors in gene therapy: their current status and future potential. Arch. Immunol. Ther. Exp. (Warsz.). 58, 107-119 (2010).
9. Palmer, D. & Ng, P. Improved system for helper-dependent adenoviral vector production. Mol. Ther. 8, 846-852 (2003).
10. Freedman, J. D. et al. Oncolytic adenovirus expressing bispecific antibody targets T-cell cytotoxicity in cancer biopsies. EMBO Mol. Med 9, 1067-1087 (2017).
11. Alemany, R. et al. Blood clearance rates of adenovirus type 5 in mice. J. Gen. Virol. 81, 2605-2609 (2000).
12. Alonso-Padilla, J. et al. Development of novel adenoviral vectors to overcome challenges observed with HAdV-5-based constructs. Mol. Ther. 24, 6-16 (2016).
13. Wohlfart, C. Neutralization of adenoviruses: kinetics, stoichiometry, and mechanisms. J. Virol. 62, 2321-2328 (1988).
14. Suomalainen, M. & Greber, U. F. Uncoating of non-enveloped viruses. Curr. Opin. Virol. 3, 27-33 (2013).
15. McEwan, W. A. et al. Intracellular antibody-mediated immunity and the role of TRIM21. Bioessays 33, 803-809 (2011).
16. Mallery, D. L. et al. Antibodies mediate intracellular immunity through tripartite motif-containing 21 (TRIM21). Proc. Natl. Acad. Sci. USA 107, 19985-19990 (2010).
17. Cichon, G. et al. Complement activation by recombinant adenoviruses. Gene Ther. 8, 1794-1800 (2001).
18. Xu, Z. et al. Clearance of adenovirus by Kupffer cells is mediated by scavenger receptors, natural antibodies, and complement. J. Virol. 82, 11705-11713 (2008).
19. Xu, Z. et al. Coagulation factor X shields adenovirus type 5 from attack by natural antibodies and complement. Nat. Med. 19, 452-457 (2013).
20. Waddington, S. N. et al. Adenovirus serotype 5 hexon mediates liver gene transfer. Cell 132, 397-409 (2008).
21. Ma, J. et al. Manipulating adenovirus hexon hypervariable loops dictates immune neutralisation and coagulation factor X-dependent cell interaction in vitro and in vivo. PLoS Pathog. 11, e1004673 (2015).
22. Doronin, K. et al. Coagulation factor X activates innate immunity to human species C adenovirus. Science 338, 795-798 (2012).
23. Prill, J. M. et al. Traceless bioresponsive shielding of adenovirus hexon with HPMA copolymers maintains transduction capacity in vitro and in vivo. PLoS ONE 9, e82716 (2014).
24. Krutzke, L. et al. Substitution of blood coagulation factor X-binding to Ad5 by position-specific PEGylation: preventing vector clearance and preserving infectivity. J. Control. Release 235, 379-392 (2016).
25. Chen, C. Y. et al. Targeting adenoviruses with factor x-single-chain antibody fusion proteins. Hum. Gene Ther. 21, 739-749 (2010).
26. Bergelson, J. M. et al. Isolation of a common receptor for Coxsackie B viruses and adenoviruses 2 and 5. Science 275, 1320-1323 (1997).
27. Wickham, T. J. et al. Integrins alpha v beta 3 and alpha v beta 5 promote adenovirus internalization but not virus attachment. Cell 73, 309-319 (1993).
28. Greber, U. F. et al. Stepwise dismantling of adenovirus 2 during entry into cells. Cell 75, 477-486 (1993).
29. Burckhardt, C. J. et al. Drifting motions of the adenovirus receptor CAR and immobile integrins initiate virus uncoating and membrane lytic protein exposure. Cell Host Microbe 10, 105-117 (2011).
30. Luisoni, S. et al. Co-option of membrane wounding enables virus penetration into cells. Cell Host Microbe 18, 75-85 (2015).
31. Lütschg, V. et al. Chemotactic antiviral cytokines promote infectious apical entry of human adenovirus into polarized epithelial cells. Nat. Commun. 2, 391 (2011).
32. Suomalainen, M. et al. A direct and versatile assay measuring membrane penetration of adenovirus in single cells. J. Virol. 87, 12367-12379 (2013).
33. Everts, M. & Curiel, D. T. Transductional targeting of adenoviral cancer gene therapy. Curr. Gene Ther. 4, 337-346 (2004).
34. Dreier, B. et al. Development of a generic adenovirus delivery system based on structure-guided design of bispecific trimeric DARPin adapters. Proc. Natl. Acad. Sci. USA 110, E869-E877 (2013).
35. Varghese, R. et al. Postentry neutralization of adenovirus type 5 by an antihexon antibody. J. Virol. 78, 12320-12332 (2004).
36. Parker, A. L. et al. Multiple vitamin K-dependent coagulation zymogens promote adenovirus-mediated gene delivery to hepatocytes. Blood 108, 2554-2561 (2006).
37. Alba, R. et al. Identification of coagulation factor (F)X binding sites on the adenovirus serotype 5 hexon: effect of mutagenesis on FX interactions and gene transfer. Blood 114, 965-971 (2009).
38. Bradshaw, A. C. et al. Requirements for receptor engagement during infection by adenovirus complexed with blood coagulation factor X. PLoS Pathog. 6, e1001142 (2010).
39. Senzer, N. N. et al. Phase II clinical trial of a granulocyte-macrophage colony-stimulating factor-encoding, second-generation oncolytic herpesvirus in patients with unresectable metastatic melanoma. J. Clin. Oncol. 27, 5763-5771 (2009).
40. Mombaerts, P. et al. RAG-1-deficient mice have no mature B and T lymphocytes. Cell 68, 869-877 (1992).
41. Koski, A. et al. Systemic adenoviral gene delivery to orthotopic murine breast tumors with ablation of coagulation factors, thrombocytes and Kupffer cells. J. Gene Med. 11, 966-977 (2009).
42. Ewert, S. et al. Stability improvement of antibodies for extracellular and intracellular applications: CDR grafting to stable frameworks and structure-based framework engineering. Methods 34, 184-199 (2004).
43. Forrer, P. et al. Kinetic stability and crystal structure of the viral capsid protein SHP. J. Mol. Biol. 344, 179-193 (2004).
44. Thorner, A. R. et al. Age dependence of adenovirus-specific neutralizing antibody titers in individuals from sub-Saharan Africa. J. Clin. Microbiol. 44, 3781-3783 (2006).
45. Au, T. et al. Minimal hepatic toxicity of Onyx-015: spatial restriction of coxsackie-adenoviral receptor in normal liver. Cancer Gene Ther. 14, 139-150 (2007).
46. Freytag, S. O. et al. Prostate cancer gene therapy clinical trials. Mol. Ther. 15, 1042-1052 (2007).
47. Marino, N. et al. Development of a versatile oncolytic virus platform for local intra-tumoural expression of therapeutic transgenes. PLoS ONE 12, e0177810 (2017).
48. Khare, R. et al. Identification of adenovirus serotype 5 hexon regions that interact with scavenger receptors. J. Virol. 86, 2293-2301 (2012).
49. Fasbender, A. et al. Complexes of adenovirus with polycationic polymers and cationic lipids increase the efficiency of gene transfer in vitro and in vivo. J. Biol. Chem. 272, 6479-6489 (1997).
50. Choi, J. W. et al. pH-sensitive oncolytic adenovirus hybrid targeting acidic tumor microenvironment and angiogenesis. J. Control Release 205, 134-143 (2015).
51. Subr, V. et al. Coating of adenovirus type 5 with polymers containing quaternary amines prevents binding to blood components. J. Control Release 135, 152-158 (2009).
52. Wortmann, A. et al. Fully detargeted polyethylene glycol-coated adenovirus vectors are potent genetic vaccines and escape from pre-existing anti-adenovirus antibodies. Mol. Ther. 16, 154-162 (2008).
53. Wang, I. H. et al. Tracking viral genomes in host cells at single-molecule resolution. Cell Host Microbe 14, 468-480 (2013).
54. Lubich, C. et al. The mystery of antibodies against polyethylene glycol (PEG)-what do we know? Pharm. Res. 33, 2239-2249 (2016).
55. Campos, S. K. & Barry, M. A. Comparison of adenovirus fiber, protein IX, and hexon capsomeres as scaffolds for vector purification and cell targeting. Virology 349, 453-462 (2006).
56. Lopez-Gordo, E. et al. Defining a novel role for the coxsackie and adenovirus receptor in human adenovirus serotype 5 transduction in vitro in the presence of mouse serum. J. Virol. 91, e02487-16 (2017).
57. Schmidt, M. M. & Wittrup, K. D. A modeling analysis of the effects of molecular size and binding affinity on tumor targeting. Mol. Cancer Ther. 8, 2861-2871 (2009).
58. Roberts, D. M. et al. Hexon-chimaeric adenovirus serotype 5 vectors circumvent pre-existing anti-vector immunity. Nature 441, 239-243 (2006).
59. Sumida, S. M. et al. Neutralizing antibodies to adenovirus serotype 5 vaccine vectors are directed primarily against the adenovirus hexon protein. J. Immunol. 174, 7179-7185 (2005).
60. Uchida, K. Natural antibodies as a sensor of electronegative damage-associated molecular patterns (DAMPs). Free. Radic. Biol. Med. 72, 156-161 (2014).
61. Myers, N. D. et al. Directed evolution of mutator adenoviruses resistant to antibody neutralization. J. Virol. 87, 6047-6050 (2013).
62. Einfeld, D. A. et al. Reducing the native tropism of adenovirus vectors requires removal of both CAR and integrin interactions. J. Virol. 75, 11284-11291 (2001).
63. Koizumi, N. et al. Reduction of natural adenovirus tropism to mouse liver by fiber-shaft exchange in combination with both CAR-and alphav integrin-binding ablation. J. Virol. 77, 13062-13072 (2003).
64. Qiu, Q. et al. Impact of natural IgM concentration on gene therapy with adenovirus type 5 vectors. J. Virol. 89, 3412-3416 (2015).
65. Agarwal, P. et al. Cell-surface integrins and CAR are both essential for adenovirus type 5 transduction of canine cells of lymphocytic origin. PLoS ONE 12, e0169532 (2017).
66. Nagel, H. et al. The αvβ5 integrin of hematopoietic and nonhematopoietic cells is a transduction receptor of RGD-4C fiber-modified adenoviruses. Gene Ther. 10, 1643-1653 (2003).
67. Greber U.F. et al. in Adenovirus Methods and Protocols. Methods in Molecular Medicine, Vol. 21 (eds Wold, W.S.M.) (Springer, Totowa, NJ, 1999).
68. Berger, I. et al. Baculovirus expression system for heterologous multiprotein complexes. Nat. Biotechnol. 22, 1583-1587 (2004).
69. Rux, J. J. & Burnett, R. M. Large-scale purification and crystallization of adenovirus hexon. Methods Mol. Med. 131, 231-250 (2007).