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A recombinant bispecific single-chain antibody induces targeted, supra-agonistic CD28-stimulation and tumor cell killing.
- Source :
- European Journal of Immunology; May2003, Vol. 33 Issue 5, p1334-1340, 7p
- Publication Year :
- 2003
-
Abstract
- 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. Thelytic 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00142980
- Volume :
- 33
- Issue :
- 5
- Database :
- Complementary Index
- Journal :
- European Journal of Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 61986814
- Full Text :
- https://doi.org/10.1002/eji.200323322