T-knife Therapeutics Announces New TCR-T Program Targeting KRAS G12V and Presents Data at the American Association for Cancer Research (AACR) Annual Meeting
T-knife Therapeutics, Inc., a biopharmaceutical company dedicated to developing novel therapeutics to fight cancer, today announced it is advancing its second TCR-T program, TK-2504, toward the clinic and presented preclinical data on its ability to generate novel TCRs targeting the KRASG12V antigen. The poster titled, “Generating optimal-affinity T cell receptors targeting the shared neoantigen KRASG12V using the humanized TCR transgenic mouse platform HuTCR” is being presented today at the American Association for Cancer Research (AACR) Annual Meeting and will be available for 30 days on the T-knife website at www.t-knife.com.
“This is an eventful year for T-knife, filled with meaningful corporate milestones,” stated Thomas M. Soloway, Chief Executive Officer of T-knife. “Today’s announcement adds TK-2504, a new KRAS targeted TCR-T program, to our pipeline, and highlights the power of the HuTCR platform to act as a new product engine capable of generating optimal affinity and high specificity TCRs against a broad array of tumor antigens.”
Elisa Kieback, Chief Technology Officer, added “KRAS is among the most frequently mutated oncogenes, and we believe the mode of action of our TCR-Ts, which are designed to directly destroy cancer cells carrying mutated KRAS proteins, has the potential to provide a significant clinical advantage over small molecule inhibitors. We are excited to have identified novel T cell receptors targeting KRASG12V that demonstrate high affinity, no detectable off-target toxicity and have the potential to be advanced to clinical development.”
The HuTCR platform is based on multiple lines of transgenic mice, each of which carries the entire human TCRα and TCRβ gene loci and expresses either single or multiple human HLAs. In this poster, multi-HLA HuTCR mice were immunized with KRASG12V peptides or the neoantigen-encoding adenovirus. After immunization, mice were screened for immune responses by in vitro restimulation of peripheral blood lymphocytes. This revealed that HLA-A11-presented epitopes were more immunogenic than epitopes presented on other HLA alleles tested. By single-cell sequencing of responding T cells, thirty distinct KRASG12V HLA-A11-restricted TCR sequences were identified. These TCRs mediated recognition of a large panel of KRASG12V-expressing cancer cell lines, as demonstrated by cytokine responses and cytotoxicity. The TCRs were further thoroughly screened for potential off-target toxicities.
TK-2504 is an HLA-A11-restricted CD8 TCR-T specific for KRASG12V. KRAS is one of the most frequently mutated oncogenes, expressed in over 25% of all cancers, and acts as a molecular switch leading to activation of many intracellular signaling pathways involved in the regulation of cell growth, cell differentiation and cell death. KRAS mutations are defined as driver mutations, meaning they are responsible for both the initiation and maintenance of cancer. Targeting driver mutations reduces the potential for the tumor to employ immune escape mechanisms, making the KRAS family an ideal target for TCR-T therapy. TK-2504 is currently in preclinical development.
About T-knife Therapeutics
T-knife is a biopharmaceutical company dedicated to developing novel therapeutics to fight cancer, initially focused on T cell receptor (TCR) engineered T cell therapies (TCR-Ts), a modality that holds the potential to generate transformative responses in patients with solid tumors. The Company’s unique approach leverages its proprietary HuTCR mouse platform, a next-generation T cell receptor and epitope discovery engine that produces fully human, tumor-specific TCRs, naturally selected in vivo for optimal affinity and high specificity.
T-knife is advancing a portfolio of TCR-T product candidates against targets with high unmet medical need, including cancer testis antigens, commonly shared tumor-driving neoantigens and oncoviral antigens. T-knife was founded by leading T-cell and immunology experts using technology developed at the Max Delbrück Center for Molecular Medicine together with Charité – Universitätsmedizin Berlin. For additional information, please visit the Company’s website at www.t-knife.com.