Targeted lysis of HIV-infected cells by natural killer cells armed and triggered by a recombinant immunoglobulin fusion protein: Implications for immunotherapy

Neil Gupta, James Arthos, Prateeti Khazanie, Tavis D. Steenbeke, Nina M. Censoplano, Eva A. Chung, Catherine C. Cruz, Margery A. Chaikin, Marybeth Daucher, Shyam Kottilil, Domenico Mavilio, Peter Schuck, Peter D. Sun, Ronald L. Rabin, Sergei Radaev, Donald Van Ryk, Claudia Cicala, Anthony S. Fauci

Research output: Contribution to journalArticle

Abstract

Natural killer (NK) cells play an important role in both innate and adaptive antiviral immune responses. The adaptive response typically requires that virus-specific antibodies decorate infected cells which then direct NK cell lysis through a CD16 mediated process termed antibody-dependent cellular cytotoxicity (ADCC). In this report, we employ a highly polymerized chimeric IgG1/IgA immunoglobulin (Ig) fusion protein that, by virtue of its capacity to extensively crosslink CD16, activates NK cells while directing the lysis of infected target cells. We employ HIV as a model system, and demonstrate that freshly isolated NK cells preloaded with an HIV gp120-specific chimeric IgG1/IgA fusion protein efficiently lyse HIV-infected target cells at picomolar concentrations. NK cells pre-armed in this manner retain the capacity to kill targets over an extended period of time. This strategy may have application to other disease states including various viral infections and cancers.

Original languageEnglish
Pages (from-to)491-497
Number of pages7
JournalVirology
Volume332
Issue number2
DOIs
Publication statusPublished - Feb 20 2005

Fingerprint

Recombinant Fusion Proteins
Natural Killer Cells
Immunotherapy
Immunoglobulins
HIV
Immunoglobulin A
Immunoglobulin G
HIV Envelope Protein gp120
Antibodies
Adaptive Immunity
Virus Diseases
Antiviral Agents
Proteins
Viruses
Neoplasms

Keywords

  • Antibody dependent cellular cytotoxicity
  • CD16
  • HIV
  • Immunotherapy
  • Natural killer cell
  • Recombinant antibody

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

Targeted lysis of HIV-infected cells by natural killer cells armed and triggered by a recombinant immunoglobulin fusion protein : Implications for immunotherapy. / Gupta, Neil; Arthos, James; Khazanie, Prateeti; Steenbeke, Tavis D.; Censoplano, Nina M.; Chung, Eva A.; Cruz, Catherine C.; Chaikin, Margery A.; Daucher, Marybeth; Kottilil, Shyam; Mavilio, Domenico; Schuck, Peter; Sun, Peter D.; Rabin, Ronald L.; Radaev, Sergei; Van Ryk, Donald; Cicala, Claudia; Fauci, Anthony S.

In: Virology, Vol. 332, No. 2, 20.02.2005, p. 491-497.

Research output: Contribution to journalArticle

Gupta, N, Arthos, J, Khazanie, P, Steenbeke, TD, Censoplano, NM, Chung, EA, Cruz, CC, Chaikin, MA, Daucher, M, Kottilil, S, Mavilio, D, Schuck, P, Sun, PD, Rabin, RL, Radaev, S, Van Ryk, D, Cicala, C & Fauci, AS 2005, 'Targeted lysis of HIV-infected cells by natural killer cells armed and triggered by a recombinant immunoglobulin fusion protein: Implications for immunotherapy', Virology, vol. 332, no. 2, pp. 491-497. https://doi.org/10.1016/j.virol.2004.12.018
Gupta, Neil ; Arthos, James ; Khazanie, Prateeti ; Steenbeke, Tavis D. ; Censoplano, Nina M. ; Chung, Eva A. ; Cruz, Catherine C. ; Chaikin, Margery A. ; Daucher, Marybeth ; Kottilil, Shyam ; Mavilio, Domenico ; Schuck, Peter ; Sun, Peter D. ; Rabin, Ronald L. ; Radaev, Sergei ; Van Ryk, Donald ; Cicala, Claudia ; Fauci, Anthony S. / Targeted lysis of HIV-infected cells by natural killer cells armed and triggered by a recombinant immunoglobulin fusion protein : Implications for immunotherapy. In: Virology. 2005 ; Vol. 332, No. 2. pp. 491-497.
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