Immunomodulation based on the target Casitas B cell lymphoma-b (Cbl-b)   Cbl-b, an E3 ubiquitin ligase, is a critical negative regulator of autoimmunity and immune tolerance in T cells: Loss of Cbl-b allows T cell activation without co-stimulation Cbl-b knock-out mice efficiently reject autologous tumors without any further treatment Cbl-b activity controls the onset of autoimmune diseases
	Therapeutic approach and achievements   Apeiron attempts to identify substances that transiently interfere with the activity of Cbl-b. Compounds or approaches that inhibit Cbl-b would lead to a more aggressive immune system and thus may enable effective vaccination strategies against cancer and other weakly immunogenic antigens and are expected to have direct antitumor activity. In contrast, compounds or approaches that enhance the activity of Cbl-b may lead to novel drugs to treat various autoimmune conditions. Presently, in collaboration with the University of Innsbruck (Oncotyrol grant program) Apeiron is engaged in transient ex-vivo silencing of Cbl-b in lymphocytes using siRNA. This approach has already led to a cellular proof of concept in human T cells.