The same core mRNA technology can be delivered to the patient using different modalities – each offering complementary opportunities for therapeutic effect.
Initially, the TriMix technology was only applied as an ex vivo product. The ex vivo product consists of dendritic cells extracted from the patient’s body, which are then, in the laboratory, modified with TriMix in combination with the specific antigen mRNA. Successively, this cellular TriMix product is reinjected as an autologous product into the patient's body.
The ex vivo TriMix cellular product has been validated in mouse models, two phase I studies and two phase IIa studies in melanoma patients (more).
Naked mRNA is delivered in vivo in the patient’s lymph node, a direct access to the machinery of the immune system. This modality is currently in phase I trial in adjuvant Melanoma. The aim is to induce a specific immune response against antigens presented as mRNA in the vaccine. Additional immune stimulation is achieved with Trimix included into the product.
A more convenient and possibly more potent immunization approach is offered by intravenous administration of the mRNA in a packaged form. Typically lipid nanoparticles are used as a formulation vehicle. This modality is currently in non-clinical development with very strong protective immune responses observed in animal models. The aim is also to induce a specific immune response against antigens presented as mRNA in the vaccine and additional immune stimulation is achieved with Trimix included into the product.
Naked or packaged mRNA is delivered directly into the patient’s tumor site, a direct access to the effector site of the therapy. This modality offers opportunities to combine tumor-lytic, tumor-modifying and immune stimulating mechanisms of action into 1 single product, and is expected to show an abscopal effect on distant tumors. Preclinical data so far confirm this hypothesis.