™ technology enables the generation of multi-specific antibody products. This unique technology overcomes the key shortcomings of conventional mono- as well as of currently developed bi-specific antibody formats.
Tribody ™ molecules are generated via the natural
in vivo heterodimerization of Fab fragments to form a scaffold, upon which two additional binding fragments, such as scFv can be incorporated. The resulting molecules are stable and easy to produce in a single batch, without the need of additional post-production reactions other than purification. Tribodies are successfully produced in standard mammalian cell technology using well established methods.
Tribodies have several advantages compared to other bi-specific formats:
- Their intermediate size (~100 kDa) between bi-specific antibody fragments and IgG molecules translates into an ideal balance between tumor penetration and half-life. Indeed, Tribodies exhibit improved tumor accumulation while maintaining an acceptable half-life compared to full IgG molecules, and a longer serum half-life and activity compared to bi-specific fragments.
- The combinatorial nature of Tribodies grants an unsurpassed versatility. Tribody molecules can be constructed using 3 distinct binders (tri-specific), 2 distinct binders with one in double copy (bivalent, bi-specific), or three copies of the same binder (trivalent).
- Tri-specificity constitutes a differentiating feature providing the unique ability to combine in one single molecule dual targeting with a T-cell or an NK-cell effector function. For this reason Tribodies have the potential to become best-in-class therapeutics to address monotherapy drug resistance and tumor heterogeneity and therefore bring clinical benefits for longer periods of time and to a larger patient population.
Tribodies also exhibit superior pharmacokinetics characteristics and improved therapeutic performances in experimental models:
- Higher stability in vitro and longer retention of biological activity in serum
- Higher binding affinity and higher effector function activation at tumor sites and at lower product concentrations
- Tribodies have similar bio-distribution patterns to IgG formats. Tribodies exhibit higher tumor accumulation rates than IgG formats, following one single injection
- Intermediate clearance time compared to the IgG and bi-specific scFv formats