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Publication type: Journal Article
Document type: Full Paper

Year: 2003

Author(s): Grosse-Hovest, L; Hartlapp, I; Marwan, W; Brem, G; Rammensee, HG; Jung, G

Title: A recombinant bispecific single-chain antibody induces targeted, supra-agonistic CD28-stimulation and tumor cell killing.

Source: Eur J Immunol. 2003; 33(5):1334-1340

Authors Vetmeduni Vienna:

Brem Gottfried

Vetmed Research Units
Institute of Animal Breeding and Genetics

Endowing tumor cells with costimulatory signals for T cell activation has emerged as a promising strategy for tumor immunotherapy. Costimulatory molecules were either transfected into tumor cells to generate vaccines or were fused, e.g. to antibodies against tumor-associated antigens, to achieve targeted T cell costimulation in vivo. Here we report the production and purification of rM28, a recombinant bispecific single-chain antibody directed to a melanoma-associated proteoglycan and to the costimulatory CD28 molecule on human T cells. We found that a dimer of the recombinant molecule, bound to tumor target cells, induced pronounced T cell activation in peripheral blood mononuclear cell preparations without additional TCR/CD3 stimulation being required. The lytic activity generated after 3 days of stimulation effectively prevented tumor cell growth. However, it was unspecific and predominantly mediated by non T cells. Our findings demonstrate that presentation of a CD28 antibody within a suitable recombinant, bispecific format may result in a "targeted supra-agonistic stimulation" of the CD28 molecule, which leads to effective tumor cell killing after induction of unspecifically lytic cells.

Keywords Pubmed: Antibodies, Bispecific/immunology*
Antibodies, Bispecific/therapeutic use
Antigens, CD28/immunology*
Cytotoxicity, Immunologic
Lymphocyte Activation
Recombinant Proteins/immunology
Tumor Cells, Cultured

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