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Antibody-targeted Photolysis of Bacteria In Vivo

Abstract

We have evaluated the efficacy of antibody-targeted photolysis to kill bacteria in vivo using specific antibacterial photosensitizer (PS) immunoconjugates. After infecting the dorsal skin in mice with Pseudomonas aeruginosa, both specific and nonspecific tin (IV) chlorin e6-monoclonal antibody conjugates were injected at the infection site. After a 15 min incubation period, the site was exposed to 630 nm light with a power density of 100 mW/cm2 for 1600 seconds. Irradiation resulted in a greater than 75% decrease in the number of viable bacteria at sites treated with a specific conjugate, whereas normal bacterial growth was observed in animals that were untreated or treated with a nonspecific conjugate. Antibody-targeted photolysis may be a selective and versatile tool for treating a variety of infections.

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References

  1. Ghose, T.I., Blair, A.H. and Kulkarni, P.N. 1983. Preparation of antibody-linked cytotoxic agents. Methods Enzymol. 93: 280–333.

    Article  CAS  Google Scholar 

  2. Youle, R.J. and Neville, D.M. 1980. Anti-Thy 1.2 monoclonal antibody linked to ricin is a potent cell-type-specific toxin. Proc. Natl. Acad. Sci. USA 77: 5483–5486.

    Article  CAS  Google Scholar 

  3. Thorpe, P.E. and Ross, W.C. 1982. The preparation and cytotoxic properties of antibody-toxin conjugates. Immunol. Rev. 62: 119–157.

    Article  CAS  Google Scholar 

  4. Pasten, I., Willingham, M.C. and Fitzgerald, D.J. 1986. Immunotoxins. Cell 47: 641–648.

    Article  Google Scholar 

  5. Baldwin, R.W., Embelton, M.J., Pimm, M.V. 1982. Monoclonal antibodies for radioimmunodetection of tumours and for targeting. Bull. Cancer 70: 103–107.

    Google Scholar 

  6. Khaw, B.A., Fallon, J.T., Strauss, H.W. and Haber, E. 1980. Myocardial infarct imaging of antibodies to canine cardiac myosin with indium-111-diethylenetriamine pentaacetic acid. Science 209: 295–297.

    Article  CAS  Google Scholar 

  7. Order, S.E., Klein, J.L., Ettinger, D., Alderson, P., Siegelman, S. and Leichner, P. 1980. Phase I-II study of radiolabeled antibody integrated in the treatment of primary hepatic malignancies. Int. J. Radiat. Oncol. Biol. Phys. 6: 703–710.

    Article  CAS  Google Scholar 

  8. Hnatowich, D., Layne, W., Childs, R., Lateigne, D., Davis, M., Griffin, T. and Doherty, P. 1983. Radioactive labeling of antibody: a simple and efficient method. Science 220: 613–615.

    Article  CAS  Google Scholar 

  9. Oldham, R.K. 1982. Monoclonal antibodies in cancer therapy. J. Clin. Oncol 1: 582–590.

    Article  Google Scholar 

  10. Morrell, E.M., Tompkins, R.G., Fischman, A.J., Strauss, H.W., Rubin, R.H., Wilkinson, R.A. and Yarmush, M.L. 1989. An autoradiographic method for quantitation of radiolabeled proteins in tissue using Indium-111. J. Nucl. Med. 30: 1538–1545.

    CAS  PubMed  Google Scholar 

  11. Morrell, E.M., Tompkins, R.G., Fischman, A.J., Strauss, H.W., Wilkinson, R.A. and Yarmush, M.L. 1990. Imaging infections with antibodies: a quantitative autoradiographic analysis. J. Immunol. Meth. 130: 39–48.

    Article  Google Scholar 

  12. Mew, D., Lum, V., Wat, C.K., Towers, G.H.N., Sin, C.H.C., Walter, R.J., Wright, W., Berns, M.W. and Levy, J.G. 1985. Ability of specific monoclonal antibodies and conventional antisera conjugated to hematoporphyrin to label and kill selected cell lines subsequent to light activation. Cancer Res. 45: 4380–4386.

    CAS  PubMed  Google Scholar 

  13. Oseroff, A.R., Ohuoha, D., Hasan, T., Bommer, J.C. and Yarmush, M.L. 1986. Antibody-targeted photolysis: selective photodestruction of human T-cell leukemia cells using monoclonal antibody-chlorin e6 conjugates. Proc. Natl. Acad. Sci. USA 83: 8744–8748.

    Article  CAS  Google Scholar 

  14. Hasan, T., Lin, A., Yarmush, D., Oseroff, A. and Yarmush, M.L. 1989. Monoclonal antibody-chromophore conjugates as selective phototoxins. J. Control. Rel. 10: 107–117.

    Article  CAS  Google Scholar 

  15. Yarmush, M.L., Thorpe, W.P., Strong, L., Toner, M. and Tompkins, R.G. 1993. Antibody targeted photolysis. Crit. Rev. Therap. Drug Carrier Sys. 10: 197–252.

    CAS  Google Scholar 

  16. Rakestraw, S.L., Tompkins, R.G. and Yarmush, M.L. 1990. Antibody-targeted photolysis: in vitro studies with Sn chlorin e6 covalently bound to monoclonal antibodies using a modified dextran carrier. Proc. Natl. Acad. Sci. USA 87: 4217–4221.

    Article  CAS  Google Scholar 

  17. Rakestraw, S.L., Tompkins, R.G. and Yarmush, M.L. 1990. Preparation and characterization of immunoconjugates for antibody targeted photolysis. Bioconj. Chem. 1: 212–221.

    Article  CAS  Google Scholar 

  18. Rakestraw, S.L., Ford, W.E., Tompkins, R.G., Rodgers, M.A., Thorpe, W.P. and Yarmush, M.L. 1992. Antibody-targeted photolysis: in vitro immunological, photophysical, and cytotoxic properties of monoclonal antibody-dextran-Sn (IV) chlorin e6 immunoconjugates. Biotechnol. Prog. 8: 30–39.

    Article  CAS  Google Scholar 

  19. Rodgers, M.A.J. and Snowden, P.T. 1982. Lifetime of singlet oxygen in liquid water as determined by time resolved infrared luminescence measurements. J. Amer. Chem. Soc. 104: 5541–5543.

    Article  CAS  Google Scholar 

  20. Foote, C.S. 1987. Type I and type II mechanisms in photodynamic action, p. 22–38. In: Light Activated Pesticides. Heitz, J.R. and Downum, K.R. (Eds.). American Chemical Society, Washington, D.C.

    Chapter  Google Scholar 

  21. Mew, D., Lum, V., Wat, C.K., Towers, G.H., Sun, C.H., Walter, R.J., Wright, W., Berns, M.W. and Levy, J.G. 1983. Photoimmunotherapy: treatment of animal tumors with tumor-specific monoclonal antibody-hemato-porphyrin conjugates. J. Immunol. 130: 1473–1477.

    CAS  PubMed  Google Scholar 

  22. Steele, J.K., Liu, D., Stammers, A.T., Whitney, S. and Levy, J.G. 1988. Suppressor deletion therapy: selective elimination of T suppressor cells in vivo using a hematoporphyrin conjugated monoclonal antibody permits animals to reject syngeneic tumor cells. Cancer Immunol. Immunother. 26: 125–131.

    Article  CAS  Google Scholar 

  23. Rubin, R.H., Young, L.S., Hansen, W.P., Nedelman, M., Wilkinson, R., Nelles, M.J., Callahan, R., Khaw, B.A. and Strauss, H.W. 1988. Specific and nonspecific imaging of localized Fischer immunotype 1 Pseudomonas aeruginosa infection with radiolabeled monoclonal antibody. J. Nucl. Med. 29: 651–656.

    CAS  PubMed  Google Scholar 

  24. Rubin, R.H., Fischman, A., Callahan, R., Khaw, B., Keech, F., Ahmad, M., Wilkinson, R. and Strauss, H.W. 1989. 111In-labeled nonspecific immunoglobin scanning in the detection of focal infection. N. Engl. J. Med. 321: 935–940.

    Article  CAS  Google Scholar 

  25. Lu, X.-M., Fischman, A.J., Stevens, E., Lee, T.T., Strong, L., Tompkins, R.G. and Yarmush, M.L. 1992. Sn-chlorin e6 antibacterial immunoconjugates: an in vitro and in vivo analysis. J. Immunol. Meth. 156: 85–99.

    Article  CAS  Google Scholar 

  26. Friedberg, J.S., Tompkins, R.G., Rakestraw, S.L., Warren, S.W., Fischman, A.J. and Yarmush, M.L. 1981. Antibody-targeted photolysis. Bacteriocidal effects of Sn (IV) chlorin e6-dextran-monoclonal antibody conjugates. Ann. N. Y. Acad. Sci. 618: 383–393.

    Article  Google Scholar 

  27. Strong, L., Tompkins, R.G., Yarmush, R.G. and Yarmush, M.L. 1994. Bacterial cell killing by antibody targeted photolysis: enhanced effect by hydroxyl radical generation. J. Control. Rel. 28: 175–186.

    Article  CAS  Google Scholar 

  28. Sande, M.A. and Mandell, G.L. 1985. Antimicrobial agents. The aminoglycosides, p.1150–1169. In: Goodman and Oilman's the Pharmacolocigal Basis of Therapeutics, 7th Edition. Gilman, A.G., Goodman, L.S., Rail, T.W, and Murad, F. (Eds). Macmillan Publishing, NY.

    Google Scholar 

  29. Yokota, T., Milenic, D.E., Whitlow, M. and Schlom, J. 1992. Rapid tumor penetration of a single-chain Fv and comparison with other immunoglobin forms. Cancer Res. 52: 3402–3408.

    CAS  Google Scholar 

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Berthiaume, F., Reiken, S., Toner, M. et al. Antibody-targeted Photolysis of Bacteria In Vivo. Nat Biotechnol 12, 703–706 (1994). https://doi.org/10.1038/nbt0794-703

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