Ira Mellman

Abstract The ability to predict T-cell receptor (TCR) specificity from sequences could transform immunotherapy, vaccine development, and our understanding of immune recognition. However, progress has been shaped by “edge cases”, in which specificity appears to be captured by simplified descriptors, such as sequence motifs or correlations between binding affinity and functional activation. Although informative, these regimes are not representative of the general mode of TCR recognition.

Abstract A fundamental challenge for cancer vaccines is to generate long-lived functional T cells that are specific for tumour antigens. Here we find that mRNA–lipoplex vaccines against somatic mutation-derived neoantigens may solve this challenge in pancreatic ductal adenocarcinoma (PDAC), a lethal cancer with few mutations.

Abstract Blockade of immune checkpoints PD-1 and TIGIT has demonstrated activity in mouse tumor models and human patients with cancer. Although these coinhibitory receptors can restrict signaling in CD8+ T cells by regulating their associated co-stimulatory receptors CD28 and CD226, the functional consequences of combining PD-1 and TIGIT blockade remain poorly characterized.