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

Grosse-Hovest, L., Hartlapp, I., Marwan, W., Brem, G., Rammensee, H. G., & Jung, G. (2003). A recombinant bispecific single-chain antibody induces targeted, supra-agonistic CD28-stimulation and tumor cell killing. European Journal of Immunology, 33(5), 1334-1340.

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Genre: Journal Article
Alternative Title : Eur. J. Immunol.

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 Creators:
Grosse-Hovest, L., Author
Hartlapp, I., Author
Marwan, W.1, Author              
Brem, G., Author
Rammensee, H. G., Author
Jung, G., Author
Affiliations:
1Oesterhelt, Dieter / Membrane Biochemistry, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565164              

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Free keywords: bispecific antibody; recombinant antibody; CD28; T cell activation; immunotherapy
 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. 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.

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Language(s): eng - English
 Dates: 2003-05
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 41363
ISI: 000182961100022
 Degree: -

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Title: European Journal of Immunology
  Alternative Title : Eur. J. Immunol.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 33 (5) Sequence Number: - Start / End Page: 1334 - 1340 Identifier: ISSN: 0014-2980