Potential Utility of Induced Translocation of Engineered Bacteria as a Therapeutic Agent for Mounting a Personalized Neoantigen-Based Tumor Immune Response

Abstract

Today, an unprecedented understanding of the cancer genome, along with major breakthroughs in oncoimmunotherapy, and a resurgence of nucleic acid vaccines against cancer are being achieved. However, in most cases, the immune system response is still insufficient to react against cancer, especially in those tumors showing low mutational burden. One way to counteract tumor escape can be the induction of bacterial translocation, a phenomenon associated with autoimmune diseases which consists of a leakage in the colonic mucosa barrier, causing the access of gut bacteria to sterile body compartments such as blood. Certain commensal or live-attenuated bacteria can be engineered in such a way as to contain nucleic acids coding for tumor neoantigens previously selected from individual tumor RNAseq data. Hypothetically, these modified bacteria, previously administered orally to a cancer patient, can be translocated by several compounds acting on colonic mucosa, thus releasing neoantigens in a systemic environment in the context of an acute inflammation. Several strategies for selecting neoantigens, suitable bacteria strains, genetic constructs, and translocation inducers to achieve tumor-specific activations of CD4 and CD8 T-cells are discussed in this hypothesis.