™ 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. With the Tribody™ technology, Biotecnol can engineer and assemble recombinant antibodies in a rational manner in order to design a chosen mechanism of action to address the killing of a specific tumour type. An anti-CD3 antibody which binds the T-cells is engineered in the Tribody™ "scaffold" where additional tumour antigens are also engineered. The Tribody™ then crosslinks tumour antigens and T-cells to initiate the tumour-cell killing process.
Tribody™ molecules are generated via the natural
in vivo heterodimerization of Fab fragments to form a scaffold (the process carried out in just one reaction in vivo and there is no chemical nor any other means of conjugation nor attachment), upon which three specific antibodies are 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 (CHO 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