T-Knife GmbH
T-knife Therapeutics is a biopharmaceutical company dedicated to developing novel therapeutics to fight cancer. The company is initially focused on T cell receptor (TCR) engineered T cell therapies (TCR-Ts), a promising modality that holds the potential to generate transformative responses in patients with solid tumors. The company’s unique approach is based on 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.
Company details
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- Business Type:
- Manufacturer
- Industry Type:
- Medical Equipment
- Market Focus:
- Globally (various continents)
About us
T-knife’s discovery engine has fueled a pipeline of TCR-T product candidates against solid tumor targets with high unmet medical need, including cancer testis antigens, oncoviral antigens and commonly shared tumor-driving neoantigens. T-knife was founded by leading T-cell and immunology experts using technology developed at the Max Delbruck Center for Molecular Medicine together with Charité – Universitätsmedizin Berlin.
Technology
TCR Therapies
T cells play a key role in the immune response by directly recognizing and eliminating infected, foreign or altered cells, such as cancer cells. To do this, they use their T-cell receptors (TCRs) to scan the surface of other cells for foreign antigens presented on Human Leukocyte Antigen (HLA) complexes.
TCR engineered T cell therapy (TCR-T) is designed to address key limitations in solid tumor therapy
Cancer cells can be recognized by mutated or viral antigens expressed only in the tumor, or self-antigens normally expressed during embryonic development and in non-somatic adult tissues. Genetic engineering of T cells with TCRs recognizing antigens aberrantly or over-expressed in cancers can redirect these T cells to the tumor, potentially offering curative responses to cancer patients.
The ability to identify potent cancer-specific TCRs has been limiting for the field of TCR-T. In the case of self-antigens, T cells bearing those TCRs are eliminated during T cell development to avoid recognition and attack of healthy tissues. For non-self tumor antigens, such as those derived from viral sequences or mutations, the very low T cell frequency in the blood has limited TCR discovery efforts.
To overcome these challenges, T-knife has developed transgenic mice (HuTCR mice) carrying the human TCRαβ gene loci and expressing multiple human HLAs. Immunizing HuTCR mice with human tumor antigens, for which mice are not tolerant, allows for the identification of both CD4+ and CD8+ T cells with TCRs that have optimized affinity / specificity profiles capable of mediating significant anti-tumor activity. The TCRs from HuTCR mice are of higher affinity for tumor self-antigens than TCRs isolated from human donors and are naturally optimized to maintain a high specificity profile, making HuTCR mice a powerful high-throughput platform for rapidly generating TCRs with best-in-class potential.