Immunotherapeutic Approaches to Mesothelioma

Abstract

Several lines of evidence indicate the activation of a host humoral and cellular response in mesothelioma patients. Tumor cells employ a number of mechanisms to promote immune tolerance and to escape host immune surveillance. These include immune checkpoints—molecules expressed on the surface of immune cells and tumor cells—that curb effector T-cell responses. The emerging category of drugs that inhibit immune checkpoints and their ligands have shown preliminary clinical activity in patients with mesothelioma. Among antigen-specific approaches, therapies targeting a tumor differentiation antigen mesothelin, which is differentially expressed in mesothelioma, are farthest along in clinical development. Included among the mesothelin-targeted immunotherapies that are under clinical investigation are immunotoxins, tumor vaccine, chimeric antigen receptor T cell, and antibody-based therapies. Of these, the monoclonal antibody amatuximab and an antibody-drug conjugate anetumab ravtansine are undergoing registration trials. Ongoing research is focused on better understanding the antitumor responses to immune-based approaches and to prospectively identify patients who are more likely to respond to these interventions. Parallel efforts are also investigating ways to therapeutically improve mesothelioma immunogenicity.