Epitopic peptides with low similarity to the host proteome: towards biological therapies without side effects.

BACKGROUND A structured analysis of the literature indicates that a low level of sequence similarity to the host proteome modulates the B cell epitope pool in the humoral immune response toward protein antigens. From a clinical point of view, low-similarity peptides might have strong repercussions for the rational development of peptide-based treatments for cancer, autoimmunity and infectious diseases. The most attractive feature of the similarity concept is that it appears to guarantee the highest specificity and lowest cross-reactivity when designing effective, safe and theoretically infallible (immuno)therapeutic tools. OBJECTIVE/METHODS This review describes the research pathway from protein- to peptide-based therapies. RESULTS/CONCLUSIONS Using the breast-cancer-associated BRCA2 protein as a model, the principle of sequence uniqueness is defined as the rationale for a pharmacological platform that might yield improved results in both patient survival and quality of life.