Attacking Tumors From All Sides: Personalized Multiplex Vaccines to Tackle Intratumor Heterogeneity

Conclusion The discovery of neoantigens and their use as tumor vaccines generated a lot of momentum in the tumor vaccination field. Personalized neoantigen vaccines hold promise in generating specific anti-tumor immune responses and durable survival benefits as emphasized by several pre-clinical and clinical studies. Especially in the last 2 years, vaccines comprising of not one, but several neoepitopes, so called multiplex neoantigen vaccines, have been developed in order to successfully increase the breadth of the anti-tumor immune response. A rationale that supports this development is obtained from recent insights into the dynamic evolution of tumors. This evolution is characterized by the time-dependent acquisition of region-specific mutations and leads to the emergence of genetically distinct tumor cell subclones within one tumor, as shown by multi-region sampling and massive parallel sequencing. These subclone-specific mutations define the neoantigen clonality, burden and therefore the total NITH, which in turn affects the potency of immunosurveillance. Tumors with a high neoantigen clonality and a low NITH show a better tumor clearance. More heterogeneous tumors with lower neoantigen clonality are more difficult to eradicate (Figure 1A). Depending on this balance between neoantigen clonality and NITH, T cells are able to reduce the diversity of subclones within a tumor and thereby actively shape the ITH. Two important factors which influence the efficacy with which ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research