Tribodies™ are multifunctional recombinant antibody derivatives, which utilise the natural in vivo heterodimerization of Fd fragments and light chains of a Fab fragment, to form a scaffold, upon which additional functions can be incorporated, such as additional binders, or cytokines, chemokines, growth factors, enzymes or protein toxins [1].
Multi-specific antibody formats, are promising therapeutic tools that target different epitopes simultaneously, as opposed to monovalent IgG molecules. However, most are small sized molecules which, although penetrate tumour tissue more rapidly than full-size antibodies, but which are also rapidly cleared from the body, usually within hours.
Tribodies were developed in order to provide a multifunctional recombinant antibody platform which had a longer serum half life than bi-specific antibodies, but which had similar tissue penetration.
Direct comparison of Tribodies and Bibodies, with scFv and bispecific scFv antibodies, show that tribodies have superior biodistribution and plasma clearance rates. Tribodies are produced in mammalian cells, where 90% of secreted Tribodies were of the correct Fd:L heterodimeric form. These are stable (due to disulfide bonds), with each of the binders retaining their specific affinities, with the bivalent Tribody having higher affinity, and higher activation of T-cell proliferation and cytotoxicity in vivo, than scFv and bispecific scFv antibodies [2].
Tribodies also retain their activity longer in serum, and also have tumour uptake rates comparable to those of full IgG molecules, but with faster clearance rates. Tribodies can be constructed using 3 different binders (tri-specific), or 2 different binders (bivalent, bispecific), or one single binder (trivalent). The versatility of the Tribody platform means that it is not limited to just antibody fragments, but any protein can in theory be attached to the Fab fragment, enabling such constructs as immunocytokines or immunotoxins. Furthermore, affinity tags can be incorporated, allowing for labelling of the constructs – e.g. for radioimmunoligands, for imaging or for radiotherapeutic purposes [3].
Biotecnol is utilising the Tribody platform in its own product pipeline development and lead optimization programme, and would also offer collaborations for use of the Tribody platform under the aegis of collaborative agreements with other companies. Such collaborations can be in-house development, production and purification of recombinant Tribody constructs for R&D and development of clinical candidate products, or pursuing collaborations with partners having proprietary targets for developing early-stage clinical candidate products. Platform out-licensing is also a possibility.
Download the Tribody™ Technology Brochure