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. 1989 Mar;86(6):1987–1991. doi: 10.1073/pnas.86.6.1987

Human immunodeficiency virus-infected T cells and monocytes are killed by monoclonal human anti-gp41 antibodies coupled to ricin A chain.

M A Till 1, S Zolla-Pazner 1, M K Gorny 1, J S Patton 1, J W Uhr 1, E S Vitetta 1
PMCID: PMC286830  PMID: 2538826

Abstract

Two human monoclonal antibodies specific for the envelope glycoprotein (gp), gp41, of the human immunodeficiency virus were conjugated to deglycosylated ricin A chain. These immunotoxins killed human immunodeficiency virus-infected H9 (T cell) and U937 (monocyte) cell lines but were nontoxic to the uninfected cell lines or to class II-positive Daudi cells. Specific killing of infected H9 cells could be completely blocked by recombinant gp160 and partially blocked by unconjugated anti-gp41 antibody but was not blocked by recombinant gp120 or human IgG demonstrating specificity for gp41. The specific toxicity of the immunotoxins for infected U937 cells was markedly potentiated by chloroquine.

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Selected References

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  1. Barré-Sinoussi F., Chermann J. C., Rey F., Nugeyre M. T., Chamaret S., Gruest J., Dauguet C., Axler-Blin C., Vézinet-Brun F., Rouzioux C. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science. 1983 May 20;220(4599):868–871. doi: 10.1126/science.6189183. [DOI] [PubMed] [Google Scholar]
  2. Chaudhary V. K., Mizukami T., Fuerst T. R., FitzGerald D. J., Moss B., Pastan I., Berger E. A. Selective killing of HIV-infected cells by recombinant human CD4-Pseudomonas exotoxin hybrid protein. Nature. 1988 Sep 22;335(6188):369–372. doi: 10.1038/335369a0. [DOI] [PubMed] [Google Scholar]
  3. Dietrich A. J., Nelson E. C., Kirk J. W., Zubkoff M., O'Connor G. T. Do primary physicians actually manage their patients' fee-for-service care? JAMA. 1988 Jun 3;259(21):3145–3149. [PubMed] [Google Scholar]
  4. Fulton R. J., Blakey D. C., Knowles P. P., Uhr J. W., Thorpe P. E., Vitetta E. S. Purification of ricin A1, A2, and B chains and characterization of their toxicity. J Biol Chem. 1986 Apr 25;261(12):5314–5319. [PubMed] [Google Scholar]
  5. Gallo R. C., Salahuddin S. Z., Popovic M., Shearer G. M., Kaplan M., Haynes B. F., Palker T. J., Redfield R., Oleske J., Safai B. Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS. Science. 1984 May 4;224(4648):500–503. doi: 10.1126/science.6200936. [DOI] [PubMed] [Google Scholar]
  6. Gartner S., Markovits P., Markovitz D. M., Betts R. F., Popovic M. Virus isolation from and identification of HTLV-III/LAV-producing cells in brain tissue from a patient with AIDS. JAMA. 1986 Nov 7;256(17):2365–2371. [PubMed] [Google Scholar]
  7. Gelderblom H. R., Reupke H., Pauli G. Loss of envelope antigens of HTLV-III/LAV, a factor in AIDS pathogenesis? Lancet. 1985 Nov 2;2(8462):1016–1017. doi: 10.1016/s0140-6736(85)90570-7. [DOI] [PubMed] [Google Scholar]
  8. Golding H., Robey F. A., Gates F. T., 3rd, Linder W., Beining P. R., Hoffman T., Golding B. Identification of homologous regions in human immunodeficiency virus I gp41 and human MHC class II beta 1 domain. I. Monoclonal antibodies against the gp41-derived peptide and patients' sera react with native HLA class II antigens, suggesting a role for autoimmunity in the pathogenesis of acquired immune deficiency syndrome. J Exp Med. 1988 Mar 1;167(3):914–923. doi: 10.1084/jem.167.3.914. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gorny M. K., Gianakakos V., Sharpe S., Zolla-Pazner S. Generation of human monoclonal antibodies to human immunodeficiency virus. Proc Natl Acad Sci U S A. 1989 Mar;86(5):1624–1628. doi: 10.1073/pnas.86.5.1624. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Knowles P. P., Thorpe P. E. Purification of immunotoxins containing ricin A-chain and abrin A-chain using blue sepharose CL-6B. Anal Biochem. 1987 Feb 1;160(2):440–443. doi: 10.1016/0003-2697(87)90073-x. [DOI] [PubMed] [Google Scholar]
  11. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  12. Modrow S., Hahn B. H., Shaw G. M., Gallo R. C., Wong-Staal F., Wolf H. Computer-assisted analysis of envelope protein sequences of seven human immunodeficiency virus isolates: prediction of antigenic epitopes in conserved and variable regions. J Virol. 1987 Feb;61(2):570–578. doi: 10.1128/jvi.61.2.570-578.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ohkuma S., Poole B. Fluorescence probe measurement of the intralysosomal pH in living cells and the perturbation of pH by various agents. Proc Natl Acad Sci U S A. 1978 Jul;75(7):3327–3331. doi: 10.1073/pnas.75.7.3327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Pastan I., Willingham M. C., FitzGerald D. J. Immunotoxins. Cell. 1986 Dec 5;47(5):641–648. doi: 10.1016/0092-8674(86)90506-4. [DOI] [PubMed] [Google Scholar]
  15. Pinter A., Honnen W. J. A sensitive radioimmunoprecipitation assay for human immunodeficiency virus (HIV). J Immunol Methods. 1988 Sep 13;112(2):235–241. doi: 10.1016/0022-1759(88)90363-8. [DOI] [PubMed] [Google Scholar]
  16. Popovic M., Sarngadharan M. G., Read E., Gallo R. C. Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. Science. 1984 May 4;224(4648):497–500. doi: 10.1126/science.6200935. [DOI] [PubMed] [Google Scholar]
  17. Press O. W., Martin P. J., Thorpe P. E., Vitetta E. S. Ricin A-chain containing immunotoxins directed against different epitopes on the CD2 molecule differ in their ability to kill normal and malignant T cells. J Immunol. 1988 Dec 15;141(12):4410–4417. [PubMed] [Google Scholar]
  18. Press O. W., Vitetta E. S., Farr A. G., Hansen J. A., Martin P. J. Evaluation of ricin A-chain immunotoxins directed against human T cells. Cell Immunol. 1986 Oct 1;102(1):10–20. doi: 10.1016/0008-8749(86)90321-7. [DOI] [PubMed] [Google Scholar]
  19. Press O. W., Vitetta E. S., Martin P. J. A simplified microassay for inhibition of protein synthesis in reticulocyte lysates by immunotoxins. Immunol Lett. 1986 Nov 17;14(1):37–41. doi: 10.1016/0165-2478(86)90017-9. [DOI] [PubMed] [Google Scholar]
  20. Ramakrishnan S., Houston L. L. Inhibition of human acute lymphoblastic leukemia cells by immunotoxins: potentiation by chloroquine. Science. 1984 Jan 6;223(4631):58–61. doi: 10.1126/science.6318313. [DOI] [PubMed] [Google Scholar]
  21. Ranki A., Weiss S. H., Valle S. L., Antonen J., Krohn K. J. Neutralizing antibodies in HIV (HTLV-III) infection: correlation with clinical outcome and antibody response against different viral proteins. Clin Exp Immunol. 1987 Aug;69(2):231–239. [PMC free article] [PubMed] [Google Scholar]
  22. Schneider J., Kaaden O., Copeland T. D., Oroszlan S., Hunsmann G. Shedding and interspecies type sero-reactivity of the envelope glycopolypeptide gp120 of the human immunodeficiency virus. J Gen Virol. 1986 Nov;67(Pt 11):2533–2538. doi: 10.1099/0022-1317-67-11-2533. [DOI] [PubMed] [Google Scholar]
  23. Shaw G. M., Harper M. E., Hahn B. H., Epstein L. G., Gajdusek D. C., Price R. W., Navia B. A., Petito C. K., O'Hara C. J., Groopman J. E. HTLV-III infection in brains of children and adults with AIDS encephalopathy. Science. 1985 Jan 11;227(4683):177–182. doi: 10.1126/science.2981429. [DOI] [PubMed] [Google Scholar]
  24. Siliciano R. F., Lawton T., Knall C., Karr R. W., Berman P., Gregory T., Reinherz E. L. Analysis of host-virus interactions in AIDS with anti-gp120 T cell clones: effect of HIV sequence variation and a mechanism for CD4+ cell depletion. Cell. 1988 Aug 12;54(4):561–575. doi: 10.1016/0092-8674(88)90078-5. [DOI] [PubMed] [Google Scholar]
  25. Starcich B. R., Hahn B. H., Shaw G. M., McNeely P. D., Modrow S., Wolf H., Parks E. S., Parks W. P., Josephs S. F., Gallo R. C. Identification and characterization of conserved and variable regions in the envelope gene of HTLV-III/LAV, the retrovirus of AIDS. Cell. 1986 Jun 6;45(5):637–648. doi: 10.1016/0092-8674(86)90778-6. [DOI] [PubMed] [Google Scholar]
  26. Sundström C., Nilsson K. Establishment and characterization of a human histiocytic lymphoma cell line (U-937). Int J Cancer. 1976 May 15;17(5):565–577. doi: 10.1002/ijc.2910170504. [DOI] [PubMed] [Google Scholar]
  27. Till M. A., Ghetie V., Gregory T., Patzer E. J., Porter J. P., Uhr J. W., Capon D. J., Vitetta E. S. HIV-infected cells are killed by rCD4-ricin A chain. Science. 1988 Nov 25;242(4882):1166–1168. doi: 10.1126/science.2847316. [DOI] [PubMed] [Google Scholar]
  28. Till M., May R. D., Uhr J. W., Thorpe P. E., Vitetta E. S. An assay that predicts the ability of monoclonal antibodies to form potent ricin A chain-containing immunotoxins. Cancer Res. 1988 Mar 1;48(5):1119–1123. [PubMed] [Google Scholar]
  29. Vitetta E. S., Fulton R. J., May R. D., Till M., Uhr J. W. Redesigning nature's poisons to create anti-tumor reagents. Science. 1987 Nov 20;238(4830):1098–1104. doi: 10.1126/science.3317828. [DOI] [PubMed] [Google Scholar]
  30. Willey R. L., Rutledge R. A., Dias S., Folks T., Theodore T., Buckler C. E., Martin M. A. Identification of conserved and divergent domains within the envelope gene of the acquired immunodeficiency syndrome retrovirus. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5038–5042. doi: 10.1073/pnas.83.14.5038. [DOI] [PMC free article] [PubMed] [Google Scholar]

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