Cbl-b Casitas B cell lymphoma-b (Cbl-b), an E3 ubiquitin ligase, is a critical negative regulator of autoimmunity and immunotolerance in T cells. The crucial role of Cbl-b has been demonstrated by Penninger and his group in knock-out mice: Cbl-b activity controls the onset of auto-immune diseases Loss of Cbl-b allows T cell activation without co-stimulation Cbl-b knock-out mice efficiently reject autologous tumors without any further treatment.
	Therapeutic approach Apeiron attempts to identify substances that transiently interfere with the activity of Cbl-b. Compounds that inhibit Cbl-b will lead to a more aggressive immune system and thus may enable effective vaccination strategies against cancer and other weakly immunogenic antigens. Such compounds also may have direct antitumor activity.   Compounds that enhance the activity of Cbl-b may lead to novel drugs that can be used to treat various autoimmune conditions. Two approaches have been initiated: Transient ex-vivo silencing of Cbl-b in T-cells with siRNA Identification of low molecular compounds that interfere with Cbl-b activity, using highthroughput screening.