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Publication type: Journal Article
Document type: Full Paper

Year: 2005

Author(s): Grosse-Hovest, L; Wick, W; Minoia, R; Weller, M; Rammensee, HG; Brem, G; Jung, G

Title: Supraagonistic, bispecific single-chain antibody purified from the serum of cloned, transgenic cows induces T-cell-mediated killing of glioblastoma cells in vitro and in vivo.

Source: Int J Cancer. 2005; 117(6):1060-1064

Authors Vetmeduni Vienna:

Brem Gottfried

Vetmed Research Units
Institute of Animal Breeding and Genetics

Here we characterize the antitumor activity of a recombinant bispecific single-chain antibody isolated from the serum of cloned transgenic cows. The antibody, termed r28M, is directed to a melanoma-associated proteoglycan, also expressed on glioblastoma cells, and to human CD28. Bound to tumor cells, r28M induced exceedingly efficient supraagonistic T-cell activation via the CD28 molecule without an additional stimulus via the TCR/CD3 complex. In vitro, T cells and NK cells contributed to tumor cell killing after r28M-mediated activation of peripheral blood mononuclear cells. However, NK activity depended on T-cell-derived cytokines. In vivo, r28M markedly inhibited the growth of human glioblastoma cells in nude mice. The serum half-life of the protein after i.v. injection was approximately 6 hr. Thus, r28M is unique not only in inducing supraagonistic CD28-mediated T-cell activation against tumor cells in vitro and in vivo, it also meets 2 additional requirements that are critical for clinical application: a relatively long serum half-life and the possibility of obtaining large amounts of active material from cloned transgenic livestock.

Keywords Pubmed: Animals
Animals, Genetically Modified/immunology*
Antibodies, Bispecific/blood*
Antigens, CD28/immunology*
Antigens, Neoplasm/immunology*
Cell Division/immunology
Killer Cells, Natural/immunology*
Lymphocyte Activation/immunology
Mice, Inbred C57BL
Mice, Nude
Neoplasm Transplantation

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