NEW YORK – T-knife Therapeutics said Thursday that the first patients with MAGE-A1-positive solid tumors have received its T-cell receptor therapy TK-8001 in a Phase I/II trial.
The therapy was developed using transgenic mice carrying the human TCRαB gene expressing human leukocyte antigens. The mice are immunized with human tumor antigens resulting in induction of CD4+ and CD8+ T cells with T-cell receptors (TCRs) that are specific for a tumor antigen, or, in the case of TK-8001, specific to MAGE-A1. This approach avoids the limitations of human-derived TCRs, which are difficult to obtain and have low affinity because the body eliminates T cells bearing self-antigens such as MAGE-A1. The San Francisco- and Berlin-based company has developed the transgenic mice as a platform for rapidly generating TCRs dubbed MyT.
The Phase I portion of the IMAG1NE trial will evaluate safety and tolerability of TK-8001 at escalating doses in six to 18 patients with MAGE-A1-positive advanced or metastatic solid tumors that either have no available therapeutic options or are non-curable. In Phase II, up to 30 patients will be evaluated at the recommended dose determined in Phase I for efficacy and safety.
In preclinical studies, TK-8001 showed in vitro serial tumor cell-killing activity and in vivo anti-tumor activity compared to a TCR therapy derived from human donors.
"Our IMAG1NE trial combines a TCR with best-in-class potential, manufacturing designed to select the most potent T cells, and biomarker-guided patient selection criteria that seeks to enroll those patients that we believe have the highest likelihood of safe, deep, and durable responses to TK-8001," T-knife Chief Medical Officer Eugen Leo said in a statement.