Developing neoantigen-targeted T cell–based treatments for solid tumors
Cet article passe en revue les progrès réalisés dans le développement d'immunothérapies à base de lymphocytes T ciblant des antigènes tumoraux puis analyse les défis à relever pour améliorer l'efficacité de ces immunothérapies
Stimulating an immune response against cancer through adoptive transfer of tumor-targeting lymphocytes has shown great promise in hematological malignancies, but clinical efficacy against many common solid epithelial cancers remains low. Targeting ‘neoantigens’—the somatic mutations expressed only by tumor cells—might enable tumor destruction without causing undue damage to vital healthy tissues. Major challenges to targeting neoantigens with T cells include heterogeneity and variability in antigen processing and presentation of targets by tumors, and an incomplete understanding of which T cell qualities are essential for clinically effective therapies. Finally, the prospect of targeting somatic tumor mutations to promote T cell destruction of cancer must contend with the biology that not all tumor-expressed ‘neoepitopes’ actually generate neoantigens that can be functionally recognized and provoke an effective immune response. In this Review, we discuss the promise, progress and challenges for improving neoantigen-targeted T cell–based immunotherapies for cancer.
Nature Medicine 2019