Human K/natural killer cells targeted with hetero-cross-linked antibodies specifically lyse tumor cells in vitro and prevent tumor growth in vivo

J. A. Titus, P. Perez, Andreas Kaubisch, M. A. Garrido, D. M. Segal

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Abstract

We have induced fresh peripheral blood K/natural killer cells to lyse a variety of target cells by coating them with anti-Fcγ receptor (anti-FcγR) (CD16) antibody hetero-cross-linked with anti-target cell antibody. The cytotoxic cell mediating this activity is different, as judged by depletion studies, from the CD3+,CD8+ T cell which is targeted by anti-CD3 cross-linked to anti-target cell antibody. Targeted K cell activity from some donors is enhanced by exposure to interleukin 2 but not interferon-γ; other donors exhibit high amounts of this activity without stimulation. Specificity of lysis mediated by targeted K cells is dictated by the specificity of the anti-target cell antibody within the heteroconjugate, and bystander cells are not lysed by targeted K cells. Hetero-cross-linked antibodies containing anti-histocompatibility leukocyte antigen class I instead of anti-FcγR (CD16) do not promote lysis, suggesting that the bridging of the target cell to FcγR on the K cell is required to activate the lytic process. Lysis mediated by targeted K cells is much less inhibitable by polymerized IgG than is classical antibody-dependent cellular cytotoxicity. Fresh human melanoma cells are lysed specificaly by K cells coated with anti-FcγR (CD16) cross-linked to the 96.5 anti-melanoma antibody. In vivo, targeted K cells prevent tumor growth at low effector to target ratios in Winn-type tumor neutralization assays. Targeted K cells may therefore provide a new immunotherapeutic approach for the destruction of detrimental cells, such as tumor and virally infected cells.

Original languageEnglish (US)
Pages (from-to)3153-3158
Number of pages6
JournalJournal of Immunology
Volume139
Issue number9
StatePublished - 1987
Externally publishedYes

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Natural Killer Cells
Antibodies
Growth
Neoplasms
Fc Receptors
In Vitro Techniques
Anti-Idiotypic Antibodies
Melanoma
Histocompatibility Antigens Class I
HLA Antigens
Interferons
Interleukin-2

ASJC Scopus subject areas

  • Immunology

Cite this

Human K/natural killer cells targeted with hetero-cross-linked antibodies specifically lyse tumor cells in vitro and prevent tumor growth in vivo. / Titus, J. A.; Perez, P.; Kaubisch, Andreas; Garrido, M. A.; Segal, D. M.

In: Journal of Immunology, Vol. 139, No. 9, 1987, p. 3153-3158.

Research output: Contribution to journalArticle

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AU - Garrido, M. A.

AU - Segal, D. M.

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