Characterizing the T cell response to a personalized cancer vaccine

Recent technological advances in sequencing and mRNA vaccines have allowed for the potential new immunotherapy strategy of personalized cancer vaccines. A patient’s primary tumor can

be resected and sequenced to computationally identify mutated, tumor-specific peptide fragments that are likely to generate a T cell immune response. These putative targets, called neoantigens, can then be used to design a custom mRNA vaccine against the patient’s specific cancer. In collaboration with Genentech and BioNtech, we recently completed and published a phase 1 trial for a personalized cancer vaccine in pancreatic cancer (Rojas et al., Nature 2023).

In this talk I will discuss how to leverage T cell receptor (TCR) repertoire sequencing to characterize and monitor responses to the vaccine. Serial bulk TCR sequencing facilitates the identification and frequency tracking of vaccine responsive T cell clones while paired single cell RNA-TCR sequencing enables phenotyping of the same clones. Together, these data show that patients can mount a durable, long-lived response to the vaccine.