i-TNT™ Platform
Vaxiion’s i-TNT™ platform is designed to generate products that utilize the well established integrin-binding protein “invasin” to target certain beta1 integrins and to stimulate receptor-mediated endocytosis. Key beta1 integrins targeted by invasin play an important role in many aspects of tumor development including metastasis and tumor angiogenesis. As such, products generated by the i-TNT™ platform will simultaneously target and deliver protein toxins, along with the important endosomal disruption agent, selectively to solid tumors and tumor vasculature. As shown in the image to the right, i-TNT™ platform minicells (fluorescently labeled) demonstrate very robust targeting and uptake into beta1 integrin expressing mammalian cells.
a-TNT™ Platform
Vaxiion’s a-TNT™ platform brings with it the potential of attaching any IgG antibody isotype to the surface of minicells that contain the protein toxin and endosomal-disruption agent. The versatility provided by the a-TNT™ platform makes it possible to test a wide array of potential product opportunities in parallel, providing much higher screening throughput.
Any a-TNT™ product arising from the a-TNT™ platform will contain two components: (i) the antibody of choice and (ii) the minicell delivery/payload vehicle. The minicell component will be manufactured separately and will be engineered to contain the protein toxin payload, the endosomal disruption agent, and a proprietary minicell surface antibody anchor. These “antibody ready” minicells will then be combined with the antibody of choice and made ready for use by using a simplified Add, Wash, and Display approach. The final prototypical a-TNT™ product is depicted in the diagram to the right.
Vaxiion has two Targeted
Nano-Toxin (TNT™) platforms under development; the i-TNT™ platform and the a-TNT™
platform (descriptions of each below). Each platform is designed around
minicells, an ideal delivery vehicle that can be programmed to target and selectively
deliver potent protein toxins directly to tumors and/or tumor vasculature and combines
the selective targeting features of antibody-drug
conjugates with the higher payload capacity of nanopolymeric and liposomal
formulations. Protein toxins are a very attractive therapeutic modality for the treatment of cancer as they are not
susceptible to conventional multi-drug resistance mechanisms and are equally
potent at each stage of the cell cycle.
The key competitive advantage offered by both TNT™ platforms is the incorporation of an endosomal disruption feature. This critical enabling feature greatly enhances overall efficacy by facilitating more efficient transfer of protein toxins to the cytosol of targeted cells and differentiates Vaxiion’s TNT™ targeted delivery platforms from competing approaches.