Chimeric anti-mesothelin receptor in tandem with the interleukin receptor (CAR-T anti-MSLN/ILR2) production in t lymphocytes for therapeutic use in patients with positive mesothelin expression tumors

Abstract

One of the biggest challenges of cancer treatments is that at some point tumor cells might become refractory, or after some time free from the disease, the patient may relapse. Thus, there is a great demand for new methods in cancer treatment, since conventional therapies such as surgery, radiation and chemotherapy cannot guarantee a cure for all patients. Celluris operates in the immunotherapy area, using CAR-T technology. This solution is being considered a paradigm shift in cancer treatment, since it empowers the patient's own cells to fight tumor cells. Our objective in this proposal is to produce chimeric receptor for MSLN antigen and test its functionality for further application in patients with MSLN-positive solid tumors. For that, we will produce lentivirus containing the expression cassette for MSLN in HEK293T cells, then transduce this vector into T cells and verify the functionality of our CAR-T through binding to the specific antigen, bound to fluorochrome. There are about 650 clinical trials around the world with this technology, and the results have been very promising, with high success rates. The FDA approved in 2018 the use of CAR-T from Novartis and later another from kite. Here in Brazil, Anvisa has already paved the entire regulatory path for the use of advanced cell therapies, making the possibility of these therapies increasingly approaching patients, who in many cases have no alternative. For the development of this new technology, we have two important partnerships, namely the Sheba Tel Hashomer City of Health Research Center/Center, elected as one of the ten best hospitals in the world by Newsweek, located in Israel, and Oswaldo Cruz Hospital. (AU)