Contact

  • Academic
    llima23@stanford.edu
    University - Student Department: Bioengineering Position: Graduate

Additional Info

  • Mail Code: 4245

All Publications

  • Library-based single-cell analysis of CAR signaling reveals drivers of in vivo persistence. bioRxiv : the preprint server for biology Perez, C. R., Garmilla, A., Nilsson, A., Baghdassarian, H. M., Gordon, K. S., Lima, L. G., Smith, B. E., Maus, M. V., Lauffenburger, D. A., Birnbaum, M. E. 2024

    Abstract

    The anti-tumor function of engineered T cells expressing chimeric antigen receptors (CARs) is dependent on signals transduced through intracellular signaling domains (ICDs). Different ICDs are known to drive distinct phenotypes, but systematic investigations into how ICD architectures direct T cell function-particularly at the molecular level-are lacking. Here, we use single-cell sequencing to map diverse signaling inputs to transcriptional outputs, focusing on a defined library of clinically relevant ICD architectures. Informed by these observations, we functionally characterize transcriptionally distinct ICD variants across various contexts to build comprehensive maps from ICD composition to phenotypic output. We identify a unique tonic signaling signature associated with a subset of ICD architectures that drives durable in vivo persistence and efficacy in liquid, but not solid, tumors. Our findings work toward decoding CAR signaling design principles, with implications for the rational design of next-generation ICD architectures optimized for in vivo function.

    View details for DOI 10.1101/2024.04.29.591541

    View details for PubMedID 38746119

    View details for PubMedCentralID PMC11092467