Probiotic-guided CAR-T cells for solid tumor targeting

Science. 2023 Oct 13;382(6667):211-218. doi: 10.1126/science.add7034. Epub 2023 Oct 12.


A major challenge facing tumor-antigen targeting therapies such as chimeric antigen receptor (CAR)-T cells is the identification of suitable targets that are specifically and uniformly expressed on heterogeneous solid tumors. By contrast, certain species of bacteria selectively colonize immune-privileged tumor cores and can be engineered as antigen-independent platforms for therapeutic delivery. To bridge these approaches, we developed a platform of probiotic-guided CAR-T cells (ProCARs), in which tumor-colonizing probiotics release synthetic targets that label tumor tissue for CAR-mediated lysis in situ. This system demonstrated CAR-T cell activation and antigen-agnostic cell lysis that was safe and effective in multiple xenograft and syngeneic models of human and mouse cancers. We further engineered multifunctional probiotics that co-release chemokines to enhance CAR-T cell recruitment and therapeutic response.

MeSH terms

  • Animals
  • Antigens, Neoplasm / immunology
  • Breast Neoplasms* / therapy
  • Cell Engineering
  • Colorectal Neoplasms* / therapy
  • Escherichia coli* / genetics
  • Escherichia coli* / immunology
  • Humans
  • Immunotherapy, Adoptive* / methods
  • Lymphocyte Activation
  • Mice
  • Probiotics* / therapeutic use
  • Receptors, Chimeric Antigen* / immunology
  • T-Lymphocytes / immunology
  • Xenograft Model Antitumor Assays


  • Receptors, Chimeric Antigen
  • Antigens, Neoplasm