Immune cells are generated to keep our bodies healthy. To combat disease, our bodies initiate two separate waves of immunity. The first wave, known as innate immunity, is a generalizable response that tries to inhibit pathogens and stop disease progression. The second wave, known as adaptive immunity, is more specific and includes T and B cells. Both cell types generate a response that directly targets the invading pathogen. T cells are a specialized population of cells that are responsible for identifying and eliminating disease. Once the cell recognizes the pathogen, it is activated, and more disease-specific immune cells are created.
Immunotherapy is a type of treatment that directs immunity, specifically the adaptive immune response, to target cancer cells. Due to the role of T cells, many different immunotherapies work to enhance their function and efficacy. A specific immunotherapy that has improved treatment for hematologic or blood malignancies includes chimeric antigen receptor (CAR) T cell therapy. This form of immunotherapy take a patient’s T cells and engineers them to target the patient’s tumor. The engineered T cells are then reinfused back into the patient where they attack the cancer. CAR T cell therapy is effective due to its specificity. The T cells are designed to target a specific tumor protein, which avoids the immune system from attacking healthy tissue. Consequently, treatment toxicity is significantly reduced.
While CAR T cells have demonstrated strong anti-tumor response in hematologic malignancies, efficacy in solid tumors is still limited. Scientists are working to improve therapy and prolong treatment efficacy by designing stronger CAR T cells. A recent paper in Cell, by Dr. Yingxiao Wang and others, describes an approach that enhances CAR T cell fitness and allows the T cells to perform at a higher rate. Wang is the Dwight C. and Hildagarde E. Baum Chair in Biomedical Engineering and Professor of Biomedical Engineering and Molecular Microbiology & Immunology at the University of Southern California. His work focuses on developing models and therapies to treat cancer using different engineering techniques and biotechnologies.
Wang and his team have developed a new form of CAR T cell therapy using ultrasound in the tumor area. The new form of therapy, known as EchoBack-CAR T cell therapy, which functions by activating T cells using ultrasound. As a result, these CAR T cells can function for up to 5 days as opposed to the standard CAR T cell therapy, in which activation only lasts for 24 hours. This type of treatment is paradigm shifting due to its long-lasting efficacy. In the clinic a patient may need to come in for treatment every day with the standard CAR T cell therapy. The EchoBack-CAR T cell treatment would require patients to come in roughly once every two weeks.
The technology is used to switch CAR T cells on after being exposed to just 10 minutes of ultrasound pulses. Consequently, it allows CAR T cells to sense cancer in their surroundings. The team named the therapy “EchoBack” due to the echo the ultrasound uses to stimulate the cells. The activated T cells then eliminate surrounding tumors cells, which create cancer debris that further activates surrounding T cells. This positive feedback loop significantly shrinks the tumor and provides a safe and effective CAR T cell alternative to solid tumors.
Wang and others have developed an efficacious immunotherapy that can target hard-to-treat solid tumors. EchoBack CAR T cell therapy is a breakthrough in cancer treatment and has the potential to change standard-of-care therapy. The team hopes to apply this to multiple cancer types including breast cancer and retinoblastoma. Overall, this work provides a robust treatment to patients with aggressive tumors.
Paper, Cell, Yingxiao Wang, University of Southern California