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T-knife Therapeutics Presents Preclinical Data on the Anti-Tumor Activity of TK-8001 at ISCT Annual Meeting

02.06.2023 / T-knife Therapeutics, Inc., a clinical-stage biopharmaceutical company dedicated to developing T cell receptor-based immunotherapies that deliver transformational benefits to cancer patients, today announced presentation of a poster titled, ”MAGE-A1 targeting TK-8001 TCR-T cells currently being investigated in the IMAG1NE Phase 1/2 clinical trial demonstrate broad in vitro and in vivo anti-tumor activity and are superior to human-derived MAGE-A1 TCRs” at the International Society for Cell & Gene Therapy (ISCT) Annual Meeting being held from May 31 – June 3, 2023 in Paris, France.

“These preclinical findings further highlight that TCRs derived from T-knife’s unique MyTTM platform provide differentiated results when compared to TCRs isolated from human donors,” said Elisa Kieback, Ph.D., Chief Technology Officer of T-knife. “Specifically, leveraging our MyT platform, we isolated TK 8001, a naturally optimized high-affinity TCR specific for the cancer testis antigen MAGE-A1. TK-8001, has repeatedly demonstrated superior in vitro anti-tumor activity against cancer cell lines derived from a wide range of tumors and superior in vivo anti-tumor activity in a very challenging syngeneic tumor mouse model.” 

MAGE-A1-specific TCRs were isolated from MyT platform mice immunized with the MAGE-A1 epitope. Human donor-derived TCRs reactive to the same epitope were synthesized based on publicly available sequences, including a clinical-stage TCR. All TCRs were expressed in primary T cells and compared in assays measuring cytotoxicity, peptide sensitivity, T cell engraftment, IFN-γ secretion, anti-tumor response and potential to recognize and kill cancer cell lines with different expression levels of MAGE-A1. The data demonstrated that T cells expressing TCR 8001, the TCR in our lead program TK-8001, performed better than human donor-derived TCRs in all evaluated metrics, including:

  • Higher peptide sensitivity, a measure of affinity;
  • Longer cytotoxic capacities upon repeated antigen stimulation;
  • Long-term cytotoxic capacity, in a variety of different tumor types, at very low effector-to-target ratio;
  • Superior T cell engraftment, leading to significantly enhanced relapse-free survival in a challenging tumor model;
  • And higher IFN-γ secretion upon tumor cell recognition, even in instances with low levels of MAGE-A1 expression. 

About The IMAG1NE Study

The IMAG1NE Phase 1/2 trial is an accelerated dose-titration, open-label, multi-center Phase 1/2 trial designed to evaluate the safety and preliminary efficacy of TK-8001 in patients with MAGE-A1 positive solid tumors. The dose escalation part of the study is focused on the selection of the recommended Phase 2 dose to advance into the dose expansion part of the study. Once the recommended Phase 2 dose has been identified, TK-8001 will then be evaluated in the expansion part of the study.

About T-knife Therapeutics

T-knife is a clinical-stage biopharmaceutical company dedicated to developing T cell receptor-based immunotherapies that deliver transformational benefits to cancer patients, initially focused on T cell receptor (TCR) engineered T cell therapies (TCR-Ts), a modality that holds the potential to generate transformational responses in patients with solid tumors. The company’s unique approach leverages its proprietary MyT 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 specificity.

T-knife is advancing a portfolio of TCR-T product candidates against targets with high unmet medical need, including cancer testis antigens and commonly shared tumor-driving neoantigens. The company’s lead program targeting MAGE-A1 positive solid tumors is in a Phase 1/2 clinical study. T-knife was founded by leading T cell and immunology experts utilizing technology developed at the Max Delbrück Center for Molecular Medicine together with the Charité – Universitätsmedizin Berlin, and is supported by a leading group of international investors, including Andera Partners, EQT Life Sciences, RA Capital Management and Versant Ventures. For additional information, please visit the company’s website at www.t-knife.com.

Quelle: Pressemitteilung T-knife Therapeutics
For additional information, please visit the company’s website.

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