In malignant pleural mesothelioma, mesothelin – a protein that can be over expressed in many cancers – is present in 80 percent to 90 percent of all these cases. However, it is not common to see mesothelin on mesothelial cells, which allows for potential targeted treatment.
CAR T -cell therapy is a type of treatment that uses T- cells and engineered receptors in combination with one another to target cancer cells. Chimeric Antigen Receptor (CAR) is the engineered receptor that is able to bind to certain proteins within a patient’s cancer cell. T- cells are immune cells responsible for detecting abnormalities in our bodies to prevent infections. In this type of therapy, T -cells are genetically engineered to target cancer cells, in hopes to attack and kill the infection. Even though this treatment was approved by the FDA in 2017, scientists and researchers continue to study the treatment to improve its effectiveness and safety.
Steps in CAR T-cell Therapy
- First T-cell must be extracted from the patient. This is done by drawing blood and passing it through an apheresis, which sorts out the T-cells.
- The CAR is then added to the T-cells, multiplied, and given back to the patient for treatment
- CAR T-cells are then inserted back into the patient’s bloodstream, continually multiplying throughout the process
- Newly added CAR T-cells bind to and attack cancer cells
The side effects of CAR-T cell therapy can be severe because the genetically altered T-cells can sometimes send the immune system in to overdrive. This can cause high fevers, low blood pressure, and even seizures.
Recent research from the University of Notre Dame aims to improve the safety and efficacy of CART T-cell therapy by the use of nanoparticles. Nanoparticles have a variety of applications from physics, to electronics, to dietary supplements, and of course, medicine. For the purpose of enhancing CAR T-cell therapy, researchers and scientists are developing a nanoparticle that serves two functions: one side will attach to the tumor and the other will activate the CAR T-cells. Overtime, the nanoparticle will dissolve from the tumor and deactivate the CAR T-cell, acting as an “off switch,” reducing the chance of over stimulating the T-cells and the negative side effects that follow.
At the moment, scientists and researchers are studying the effects of using nanoparticles in breast cancer; however, with positive results, this technology could be used with other solid tumors such as those found in mesothelioma.
CAR T-cell research remains promising for those suffering from mesothelioma. Preliminary results in an ongoing study presented to the 2018 American Society of Gene and Cell Therapy Annual Meeting showed that CAR T-cell therapy was more effective in patients who received additional PD-1 treatment.
Early Signs of Efficacy Seen with Mesothelin CAR T-Cell Therapy
Source:
Brandi Klingerman, “Developing an ‘On and Off’ Switch for Breast Cancer Treatment,” Notre Dame Research (August 15, 2018). [Link]
