TCR2 Therapeutics has partnered with Raffit Hassan, MD, at the National Cancer Institute to test TC-210, a mesothelin-specific immunotherapy, in an ongoing Phase 1/2 clinical trial for people with advanced cancers that produce the mesothelin protein.
Mesothelin is a protein highly abundant in several solid tumors, including ovarian cancer. Its abundance is linked with poorer prognosis, and is suggested to play a role in the development of certain tumors.
While CAR T-cell therapy has shown exciting results for treating blood cancers, the response rates in solid cancer have been disappointing. That therapy consists of collecting a patient’s own T-cells and modifying them in the lab to produce a chimeric antigen receptor, or CAR, that targets a specific cancer protein. The CAR T cells are then given back to the patient by infusion.
TCR2 Therapeutic’s TC-210 was designed with a new technology, called T-cell Receptor Fusion Constructs, or TRuC-T. It aims to harness the full potential of T-cells against cancer cells.
In preclinical studies with cells and animal models of lung, ovarian and mesothelioma cancers, TC-210 showed robust anti-tumor activity. Moreover, T-cell activation and tumor clearance with TC-210 was faster than that achieved with CAR T-cell therapies targeting the mesothelin protein.
The new treatment also appears safer than CAR T-cell therapies, exhibiting lower levels of cytokine release. This means that there was a lower systemic activation of the immune system, which can bring life-threatening consequences to patients.
The ongoing Phase 1/2 trial (NCT03907852), which is recruiting patients in the U.S., is assessing the safety and efficacy of TC-210 in people with mesothelin-producing cancers who have been given prior chemotherapy.
In the Phase 1 part, researchers will determine the optimal recommended dose of TC-210. The immunotherapy’s anti-tumor activity will then be assessed in the trial’s Phase 2 part in four distinct cancer types: ovarian cancer, non-small cell lung cancer, mesothelioma, and bile duct cancer.
During the trial, NCI will be conducting studies that may improve outcomes in TC-210-treated patients. Those studies will measure potential biomarkers that determine who is more likely to respond to treatment, and identify markers of early response.
“The fundamental validation and use of mesothelin as a target in immunotherapy by Dr. Hassan and his colleagues was a major development in oncology and we are excited to collaborate with the National Cancer Institute on the first clinical trial of a TRuC-T cell against mesothelin,” Garry Menzel, PhD, president and CEO of TCR2 Therapeutics, said in a press release.
“We look forward to providing an update on the safety, efficacy and translational studies occurring at several sites from the Phase 1 portion of the Phase 1/2 trial for TC-210,” Menzel added.