Challenges in neoantigen-directed therapeutics

A fundamental prerequisite for the efficacy of cancer immunotherapy is the presence of functional, antigen-specific T cells within the tumor. Neoantigen-directed therapy is a promising strategy that aims at targeting the host’s immune response against tumor-specific antigens, thereby eradicating cancer cells. Initial forays have been made in clinical environments utilizing vaccines and adoptive cell therapy; however, many challenges lie ahead. We provide an in-depth overview of the current state of the field with an emphasis on in silico neoantigen discovery and the clinical aspects that need to be addressed to unlock the full potential of this therapy. Lybaert et al. describe the clinical challenges associated with neoantigen-based cancer treatments and response monitoring in various tumor types. The authors give an overview of the currently available neoantigen prediction pipelines, and outline the optimal workflow and available tools to identify tumor-specific neoantigens derived from all possible variant types.