A key approach to treating cancer these days is engineering immune T-cells to produce receptors on their surfaces that recognize cancer, so that the T-cells can attack it.
One engineering approach is creating CAR T-cells, with CAR standing for the chimeric antigen receptors the approach produces. TCR² Therapeutics is creating what it calls TRuC T-cells that produce a different kind of receptor. And early indications are that its approach is more effective, it said.
A single dose of its TC-201 immunotherapy eradicated mesothelioma tumors in mice, the company said, while tumors in mice treated with CAR T-cells returned after the cancer was in remission. The company said it hopes to start clinical trials of TC-210 in 2018.
In another preclinical-trial study, TCR² said its TRuC T-cells killed cancer cells in a laboratory better than CAR T-cells, and released fewer immune-stimulating proteins known as cytokines. Excess production of cytokines is often linked with the development of a life-threatening immunotherapy side effect, called cytokine release syndrome, in which the immune system becomes overactive and begins attacking healthy cells.
In addition, TRuC T-cells increased survival in mice with lymphoma, compared with CAR T-cells, the company said.
“These preclinical data represent a key milestone in the advancement of T cell therapies,” Dr. Garry Menzel, chief executive officer of TCR², said in a press release. “We show for the first time that our unique TRuC technology can potentially overcome three limitations of CAR-T in solid tumors: lack of efficacy, safety concerns, and durability.”
TRuC T-cells’ ability to outperform CAR T-cells lies in how they are engineered, TCR² said. CARs are separate from natural T-cell receptors, working in tandem with them.
TCR²’s scientists fuse antigen-binding components into the natural T-cell receptor complex, making TRuCs part of the T-cell receptor. This means the T-cells can make use of the complex signaling pathways and feedback loops in the natural cell, enhancing their ability to fight cancer.
The company presented results from its studies at the World Preclinical Congress in Boston, June 12-16.
It said the results of CAR T-cell treatment in its mesothelioma mice study echoed the results of previous research: the therapy led to the cancer regressing, but then returning. Research has also shown that what scientists call T-cell exhaustion can make CAR T-cells ineffective against solid tumors over time, TCR² said.
In contrast, mesothelioma in the mice treated with TRuCs failed to return after it went into remission.
When researchers injected additional mesothelioma cancer cells into mice treated with TRuCs, the animals did not grow new tumors, suggesting the response to the therapy is also long-lasting.
“Our strategic focus is on expanding cell therapy to solid tumors by using constructs that recruit the entire TCR and its natural signaling power,” Menzel said. “We are now on a path to the clinic in 2018 with our lead program TC-210 targeting mesothelin, a tumor antigen highly expressed in solid tumors, including ovarian, pancreatic, mesothelioma and lung cancers.”