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Immunotoxin Methods and Protocols pp 277–294Cite as

In Vivo Testing of Anti-HIV Immunotoxins

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Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 166))

Abstract

The past several years have seen great optimism resulting from the deployment of highly active antiretroviral therapies for the treatment of HIV infection. Combinations of reverse transcriptase and protease inhibitors can induce suppression of viremia, reversal of immunodeficiency state, and remission from AIDS-associated illnesses. However, long-term compliance with these drug regimens is difficult because of complicated dosing schedules, cost, and drug toxicities. The development of drug-resistant HIV has also limited the effectiveness of antiviral therapies. The evolution of drug-resistant HIV is enhanced when patient compliance drops and HIV replicates in the presence of moderate concentrations of antiviral agents. Even in patients in whom there has been complete suppression of HIV replication for several years, there are persistent reservoirs of HIV-infected cells. Cessation of therapy, or even modification of the intensive drug regimens, results in the prompt reestablishment of HIV replication. Thus, despite the great improvements made in the treatment of AIDS, there is still a need for the development of new antiviral agents, particularly ones that have different modes of action than existing antivirals.

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References

  1. Pincus, S. H., Cole, R. L., Hersh, E. M., Lake, D., Masuho, Y., Durda, P. J., and McClure, J. (1991) In vitro efficacy of anti-HIV immunotoxins targeted by various antibodies to the envelope protein. J. Immunol. 146, 4315–4324.

    PubMed  CAS  Google Scholar 

  2. Pincus, S.H. and McClure, J. (1993) Soluble CD4 enhances the efficacy of immunotoxins directed against gp41 of the human immunodeficiency virus. Proc. Natl. Acad. Sci. USA 90, 332–336.

    Article  PubMed  CAS  Google Scholar 

  3. Pincus, S. H., Wehrly, K., Cole, R., Fang, H., Lewis, G. K., McClure, J., et al. (1996) In vitro effects of anti-HIV immunotoxins directed against multiple epitopes on the HIV-1 envelope glycoprotein gp160. AIDS Res. Hum. Retrovirus 12, 1041–1051.

    Article  CAS  Google Scholar 

  4. Pincus, S.H. (1996) Therapeutic potential of anti-HIV immunotoxins. Antiviral Res. 33, 1–9.

    Article  PubMed  CAS  Google Scholar 

  5. Ashorn, P., Moss, B., Weinstein, J. N., Chaudhary, V. K., FitzGerald, D. J., Pastan, I., et al. (1990) Elimination of infectious human immunodeficiency virus from human T-cell cultures by synergistic action of CD4-Pseudomonas exotoxin and reverse transcriptase inhibitors. Proc. Natl. Acad. Sci. USA 87, 8889–8893.

    Article  PubMed  CAS  Google Scholar 

  6. Chaudhary, V. K., Mizukami, T., Fuerst, T. R., FitzGerald, D. J., Moss, B., Pastan, I., et al. (1988) Selective killing of HIV-infected cells by recombinant human CD4-Pseudomonas exotoxin hybrid protein. Nature 335, 369–372.

    Article  PubMed  CAS  Google Scholar 

  7. Berger, E. A., Clouse, K. A., Chaudhary, V. K., Chakrabarti, S., FitzGerald, D. J., Pastan, I., et al. (1989) CD4-Pseudomonas exotoxin hybrid protein blocks the spread of human immunodeficiency virus infection in vitro and is active against cells expressing the envelope glycoproteins from diverse primate immunodeficiency retroviruses. Proc. Natl. Acad. Sci. USA 86, 9539–9543.

    Article  PubMed  CAS  Google Scholar 

  8. Ashorn, P., Englund, G., Martin, M. A., Moss, B., and Berger, E. A. (1991) Anti-HIV activity of CD4-Pseudomonas exotoxin on infected primary human lymphocytes and monocyte/macrophages. J. Infect. Dis. 163, 703–709.

    PubMed  CAS  Google Scholar 

  9. Berger, E. A., Moss, B., and Pastan, I. (1998) Reconsidering targeted toxins to eliminate HIV infection: you gotta have HAART. Proc. Natl. Acad. Sci. USA 95, 11,511–11,513.

    Article  PubMed  CAS  Google Scholar 

  10. Finberg, R. W., Wahl, S. M., Allen, J. B., Soman, G., Strom, T. B., Murphy, J.R., et al. (1991) Selective elimination of HIV-1-infected cells with an interleukin-2 receptor-specific cytotoxin. Science 252, 1703–1705.

    Article  PubMed  CAS  Google Scholar 

  11. Bell, K. D., Ramilo, O., and Vitetta, E. S. (1993) Combined use of an immunotoxin and cyclosporine to prevent both activated and quiescent peripheral blood T cells from producing type 1 human immunodeficiency virus. Proc. Natl. Acad. Sci. USA 90, 1411–1415.

    Article  PubMed  CAS  Google Scholar 

  12. Ramilo, O., Bell, K. D., Uhr, J. W., and Vitetta, E. S. (1993) Role of CD25+ and CD25-T cells in acute HIV infection in vitro. J. Immunol. 150, 5202–5208.

    PubMed  CAS  Google Scholar 

  13. Borvak, J., Chou, C.-S., Bell, K., G. Van Dyke, Zola, H., Ramilio, O., et al. (1995) Expression of CD25 defines peripheral blood mononuclear cells with productive versus latent HIV infection. J. Immunol. 155, 3196–3204.

    PubMed  CAS  Google Scholar 

  14. Davey, R. T., Boenning, C. M., Herpin, B. R., Batts, D. H., Metcalf, J. A., Wathen, L., et al. (1994) Recombinant soluble CD4-Pseudomonas exotoxin, a novel immunotoxin, in the treatment of individuals infected with HIV. J. Infect. Dis. 170, 1180–1188.

    PubMed  Google Scholar 

  15. Ramachandran, R. V., Katzenstein, D. A., Wood, R., Batts, D.H., and Merigan, T.C. (1994) Failure of short-term CD4-PE40 infusions to reduce viral load in HIV infected individuals. J. Infect. Dis. 170, 1009–1013.

    PubMed  CAS  Google Scholar 

  16. Mosier, D.E. (1996) Small animal models for AIDS research. Lab. Animal Sci. 46, 257–265.

    CAS  Google Scholar 

  17. Bonyhadi, M. L., Rabin, L., Salimi, S., Brown, D. A., Kosek, J., McCune, J.M., et al. (1993) HIV induces thymus depletion in vivo. Nature 363, 728–732.

    Article  PubMed  CAS  Google Scholar 

  18. Mosier, D. E., Gulizia, R. J., MacIsaac, P. D., Torbett, B. E., and Levy, J. A. (1993) Rapid loss of CD4+ T cells in human-PBL-SCID mice by noncytopathic HIV isolates. Science 260, 689–691.

    Article  PubMed  CAS  Google Scholar 

  19. Pai, L. H., Batra, J. K., FitzGerald, D. J., Willingham, M. C., and Pastan, I. (1992) Antitumor effects of B3-PE and B3-LysPE40 in a nude mouse model of human breast cancer and the evaluation of B3-PE toxicity in monkeys. Cancer Res. 52, 3189–3193.

    PubMed  CAS  Google Scholar 

  20. Trail, P. A., Willner, D., Lash, S. J., Henderson, A. J., Hofstead, S., Casazza, A. M., et al. (1993) Cure of xenografted human carcinomas by BR96-doxorubicin immunoconjugates. Science 261, 212–215.

    Article  PubMed  CAS  Google Scholar 

  21. Jansen, B., Vallera, D. A., Jaszcz, W. B., Nguyen, D., and Kersey, J. H. (1992) Successful treatment of human acute T-cell leukemia in SCID mice using the anti-CD7-deglycosylated ricin A-chain immunotoxin DA7. Cancer Res. 52, 1314–1321.

    PubMed  CAS  Google Scholar 

  22. Ghetie, M. A., Gordon, B. E., Podar, E.M., and Vitetta, E. S. (1996) Effect of sublethal irradiation of SCID mice on growth of B-cell lymphoma xenografts and on efficacy of chemotherapy and/or immunotoxin. Lab. Animal Sci. 46, 305–309.

    CAS  Google Scholar 

  23. Frankel, A. E., Fitzgerald, D., Siegall, C., and Press, O. W. (1996) Advances in immunotoxin biology and therapy. Cancer Res. 56, 926–932.

    PubMed  CAS  Google Scholar 

  24. Thrush, G. R., Lark, L. R., Clinchy, B. C., and Vitetta, E. S. (1996) Immunotoxins: an update. Ann. Rev. Immunol. 14, 49–71.

    Article  CAS  Google Scholar 

  25. Pincus, S.H. and Wehrly, K. (1990) AZT demonstrates anti-HIV-1 activity in persistently infected cell lines: implications for combination chemotherapy and immunotherapy. J. Infect. Dis. 162, 1233–1238.

    PubMed  CAS  Google Scholar 

  26. Fang, H. and Pincus, S. H. (1995) Unique insertion sequence and pattern of CD4 expression in variants selected with immunotoxins from human immunodeficiency virus type 1-infected T cells. J. Virol. 69, 75–81.

    PubMed  CAS  Google Scholar 

  27. Duensing, T. D., Fang, H., Dorward, D. W., and Pincus, S. H. (1995) Processing of the envelope glycoprotein gp160 in immunotoxin-resistant cell lines chronically infected with HIV-1. J. Virol. 69, 7122–7131.

    PubMed  CAS  Google Scholar 

  28. Pincus, S. H. (1999) Targeting drugs to HIV-infected cells, in Drug Targeting, Methods in Molecular Medicine, vol. 11. (Francis, G. E., ed.), Humana Press, Totowa, NJ, pp. 193–214.

    Google Scholar 

  29. Pincus, S. H., Wehrly, K., and Chesebro, B. (1991) Use of a focal infectivity assay for testing susceptibility of HIV to antiviral agents. BioTechniques 10, 336–342.

    PubMed  CAS  Google Scholar 

  30. Chesebro, B. and Wehrly, K. (1988) Development of a sensitive quantitative focal assay for human immunodeficiency virus infectivity. J. Virol. 62, 3779–3788.

    PubMed  CAS  Google Scholar 

  31. Chesebro, B., Wehrly, K., Metcalf, J., and Griffin, D. E. (1991) Use of a new CD4-positive HeLa cell clone for direct quantitation of infectious human immunodeficiency virus from blood cells of AIDS patients. J. Infect. Dis. 163, 64–70.

    PubMed  CAS  Google Scholar 

  32. Platt, E. J., Wehrly, K., Kuhmann, S. R., Chesebro, B., and Kabat, D. (1998) Effects of CCR5 and CD4 cell surface concentrations on infections by macrophage-tropic isolates of HIV-1. J. Virol. 72, 2855–2864.

    PubMed  CAS  Google Scholar 

  33. Shultz, L. D., Schweitzer, P. A., Christianson, S. W., Gott, B., Schweitzer, I. B., Tennent, B., et al. (1995) Multiple defects in innate and adaptive immunologic function in NOD/LtSz-scid mice. J. Immunol. 154, 180–191.

    PubMed  CAS  Google Scholar 

  34. Kabat, D., Kozak, S. L., Wehrly, K., and Chesebro, B. (1994) Differences in CD4 dependence for infectivity of laboratory-adapted and primary patient isolates of HIV. J. Virol. 68, 2570–2577.

    PubMed  CAS  Google Scholar 

  35. Berger, E. A., Fuerst, T. R., and Moss, B. (1988) A soluble recombinant polypeptide comprising the amino-terminal half of the extracellular region of the CD4 molecule contains an active binding site for human immunodeficiency virus. Proc. Natl. Acad. Sci. USA 85, 2357–2361.

    Article  PubMed  CAS  Google Scholar 

  36. Koyanagi, Y., Tanaka, Y., Kira, J., Ito, M., Hioki, K., Misawa, N., et al. (1997) Primary human immunodeficiency virus type 1 viremia and central nervous system invasion in a novel hu-PBL-immunodeficient mouse strain. J. Virol. 71, 2417–2424.

    PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Microbiology, Montana State University, Bozeman, MT

    Seth H. Pincus & Hua Fang

  2. Animal Resources Center, Montana StateUniversity, Bozeman, MT

    Tamera K. Marcotte

  3. Bozeman Cancer Center, Bozeman DeaconessHospital, Bozeman, MT

    Brent M. Forsyth

Authors
  1. Seth H. Pincus
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  2. Tamera K. Marcotte
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  3. Brent M. Forsyth
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  4. Hua Fang
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Editor information

Editors and Affiliations

  1. Department of Neurosurgery, University of Minnesota, Minneapolis, Minnesota

    Walter A. Hall MD

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© 2001 Humana Press Inc., Totowa, NJ

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Pincus, S.H., Marcotte, T.K., Forsyth, B.M., Fang, H. (2001). In Vivo Testing of Anti-HIV Immunotoxins. In: Hall, W.A. (eds) Immunotoxin Methods and Protocols. Methods in Molecular Biology™, vol 166. Humana Press. https://doi.org/10.1385/1-59259-114-0:277

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  • DOI: https://doi.org/10.1385/1-59259-114-0:277

  • Publisher Name: Humana Press

  • Print ISBN: 978-0-89603-775-5

  • Online ISBN: 978-1-59259-114-5

  • eBook Packages: Springer Protocols

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