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
✍ Scribed by Ludger Grosse-Hovest; Wolfgang Wick; Rosa Minoia; Michael Weller; Hans-Georg Rammensee; Gottfried Brem; Gundram Jung
- Publisher
- John Wiley and Sons
- Year
- 2005
- Tongue
- French
- Weight
- 202 KB
- Volume
- 117
- Category
- Article
- ISSN
- 0020-7136
No coin nor oath required. For personal study only.
✦ Synopsis
Abstract
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. © 2005 Wiley‐Liss, Inc.