T-knife Therapeutics has received authorization to begin a Phase 1 clinical trial of TK-6302, a CRISPR-engineered T cell therapy designed to target PRAME-expressing solid tumors.
The first-in-human ATLAS trial, authorized in Europe, will evaluate the therapy in patients with advanced PRAME-positive cancers and is expected to begin later this year.
PRAME (preferentially expressed antigen in melanoma) is a tumor-associated antigen found across multiple solid tumor types, including squamous non-small cell lung, ovarian, endometrial, skin, and triple-negative breast cancers. Its broad expression profile has made it an attractive target for T cell–based immunotherapies, although solid tumors have historically proven difficult to treat with engineered immune cells.
TK-6302 aims to address several barriers that limit the effectiveness of T cell therapies in solid tumors. The engineered cells incorporate a high-affinity receptor targeting PRAME to enhance tumor recognition and cytotoxic activity, along with additional genetic modifications intended to strengthen T-cell persistence within the tumor microenvironment.
These include a costimulatory CD8 coreceptor that engages CD4 T cells to support T-cell fitness, as well as a FAS-based checkpoint converter intended to improve engraftment and promote survival in immunosuppressive tumor environments. The therapy is produced using a non-viral CRISPR gene-editing process intended to improve T cell receptor expression and manufacturing scalability.
According to the company, preclinical studies showed sustained tumor cell killing and cytokine secretion in models designed to mimic inhibitory ligand expression in PRAME-expressing tumors. In a three-dimensional tumor spheroid model, the engineered T cells eliminated multiple rounds of tumor growth and demonstrated stronger anti-tumor activity than control cells.
“We are proud to achieve this important milestone, which enables the initiation of the Phase 1 ATLAS clinical trial and our transition to becoming a clinical-stage company,” said Thomas M. Soloway, President and Chief Executive Officer of T-knife Therapeutics.
Peggy Sotiropoulou, Chief Scientific Officer of T-knife, said the therapy was intended to improve T-cell persistence and activity in challenging tumor environments. “By bolstering T-cell fitness and persistence while overcoming tumor-mediated immune barriers, TK-6302 has the potential to deliver meaningful clinical benefit across a range of solid tumor cancers.”
If successful, the therapy could expand the reach of engineered T cell therapies into solid tumors, where durable responses have historically been more difficult to achieve than in hematologic cancers.
Newsletters
Receive the latest pharmaceutical news, personalities, education, and career development – weekly to your inbox.
