A golden era of opportunity in immunotherapy discovery and development

摘要

Our ability to dissect immune pathways with the advent of molecular, cellular, and immunological techniques has led to a significant number of breakthrough discoveries over the past quarter century that have established our current paradigms of cellular and developmental immunology. The more recent application of genome-wide genetic association scans, gene expression microarrays, and proteome analysis to interrogate human tissue has revealed the marked complexities and heterogeneity of human autoimmune diseases, as well as defined pathways that are dominant in patient subsets of diseases. As examples, the genome-wide single nucleotide polymorphism (SNP) analysis of Crohn's disease has revealed the potential importance of nucleotide oligomerization domain 2 (NOD2) and the interleukin-23 (IL-23) receptor pathways in subsets of patients, mRNA microrarray analyses have suggested the importance of interferon-regulated genes in systemic lupus erythematosus, and proteome analyses of brain plaques have implicated the clotting cascade in multiple sclerosis. This convergence of knowledge of immunologic pathways coupled "with our ability to interrogate the dysregu-lated components in human diseases has accelerated and broadened our ability to identify appropriate drug discovery targets. Indeed, this is an exciting time in drug discovery as the biologies of human diseases are being uncovered