July 14, 2024
Engineered Bacteria Manipulate Tumors

Engineered Bacteria Manipulate Tumors to Make Them Visible to Cancer-Fighting T Cells

A breakthrough approach to fighting cancer has been developed by synthetic biologists at Columbia Engineering. They have successfully engineered tumor-colonizing bacteria, or probiotics, to produce synthetic targets within tumors. These targets then direct chimeric antigen receptor T cells (CAR-T cells) to destroy the cancer cells marked by the synthetic antigens.

CAR-T cell therapy has proven successful in targeting specific antigens found on blood cells, providing a cure for patients with leukemia and lymphoma. However, it has been difficult to achieve the same success in solid tumors, such as breast and colon cancers, because these tumors contain a mix of cells that display different antigens on their surface, often shared with healthy cells in the body.

The researchers at Columbia Engineering have created a universal CAR-T cell that attacks a universal antigen by programming the tumor-seeking bacteria to paint solid tumors with a synthetic marker that the CAR-T cells can recognize. With further refinements, this platform could enable the treatment of any solid tumor type without the need to identify a specific tumor antigen, eliminating the need to generate a custom CAR-T cell product for each cancer type and each patient.

This probiotic-guided CAR-T cell platform, known as ProCAR, is the first of its kind to successfully combine engineered probiotics with CAR-T cells. It has demonstrated the first evidence of CARs responding to synthetic antigens produced directly within the tumor. The combination of tumor-homing bacteria and CAR-T cells provides a new strategy for tumor recognition and lays the foundation for engineered communities of living therapies.

The ProCAR platform has been proven to be safe and effective across multiple models of human and mouse cancers in both immunocompromised and immune-healthy mice. The presence of immunostimulatory bacteria within the tumor enhances the tumor-killing functions of human T cells.

According to Tal Danino, associate professor of biomedical engineering at Columbia Engineering, the ProCAR platform represents a new strategy for enhancing the effectiveness of CAR-T cell therapy in solid tumors. While the research phase is ongoing, this breakthrough could open up new avenues for cancer therapy.

This work was conducted in collaboration with the laboratory of Nicholas Arpaia, assistant professor of microbiology and immunology at Columbia’s Vagelos College of Physicians and Surgeons. The researchers are continuing to refine their work and plan to commence clinical trials to evaluate the platform’s safety and efficacy in human patients.

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  1. Source: Coherent Market Insights, Public sources, Desk research
  2. We have leveraged AI tools to mine information and compile it