Here we charaeterize the antitumor activity of a reconbinant bispecific single-chain antibody isolated from the serurn of cloned transgenic cows. The antibody, termed r28M, is directed to a melanoma-associated proteogiycan, aiso expressed on gliobiastoma cells, and to human CD28. Bound to tumor cells, r28M induced exceedingiy efficient supraagonistic T-cell activation via the CD28 molecule without an additional stirnulus via the TCR/CD3 complex. In vitro, T cells and NK cells conlributed to tumor cell killing after r28M-mediated activation of peripheral biood mononuclear cells. However, NK activity depended on T-cell-derived cytokines. In vivo, r28M markedly inhibited the growth of human giioblastoma cells in nude mice. The serum haif-iife of the protein after i.v. injection was approximately 6 hr. Thus, r28M Is unique not oniy in inducing supraagonistic CD28-mediated T-cell activation against tumor cells in vitro and in vivo, it aiso meets 2 additional requirements that have critical for ciinical application: a relatively long serum half-life and the possibility of obtaining large amounts of active material from cloned transgenic livestock.
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
MINOIA, Rosa;
2005-01-01
Abstract
Here we charaeterize the antitumor activity of a reconbinant bispecific single-chain antibody isolated from the serurn of cloned transgenic cows. The antibody, termed r28M, is directed to a melanoma-associated proteogiycan, aiso expressed on gliobiastoma cells, and to human CD28. Bound to tumor cells, r28M induced exceedingiy efficient supraagonistic T-cell activation via the CD28 molecule without an additional stirnulus via the TCR/CD3 complex. In vitro, T cells and NK cells conlributed to tumor cell killing after r28M-mediated activation of peripheral biood mononuclear cells. However, NK activity depended on T-cell-derived cytokines. In vivo, r28M markedly inhibited the growth of human giioblastoma cells in nude mice. The serum haif-iife of the protein after i.v. injection was approximately 6 hr. Thus, r28M Is unique not oniy in inducing supraagonistic CD28-mediated T-cell activation against tumor cells in vitro and in vivo, it aiso meets 2 additional requirements that have critical for ciinical application: a relatively long serum half-life and the possibility of obtaining large amounts of active material from cloned transgenic livestock.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.