Empowering T cells with tumor-specific T cell receptors (TCR-Ts)
Patient-derived T cells are modified for adoptive T cell therapy with selected and pre-clinically tested T cell receptors (TCRs). For chosen tumor antigens the modified T cells, so-called TCR-Ts, are generated using Medigene’s TCR-T platform, based on knowledge obtained in more than 30 years of research. Medigene’s growing portfolio of different TCR-Ts have the potential to treat broad patient populations suffering from various types of cancer.
Medigene’s TCR-T platform offers unique advantages:
- Originating from Medigene’s TCR discovery platform, TCRs with selected specificities are isolated and characterized and subsequently assessed to potentially treat various types of blood cancers and solid tumors.
- Isolated TCRs are of natural origin and are chosen to have optimal affinities and hence the TCRs do not need mutational engineering to improve their capacity to find and bind tumor cells.
- The TCR discovery platform can deliver TCRs recognizing a variety of different tumor antigens, representing either common antigens shared by tumors or patient-individual neoantigens.
- TCRs for both CD4+ and CD8+ T cells can be generated, which recognize peptide fragments presented by different HLA class I and HLA class II alleles, providing greater potential for effective treatments to larger numbers of patients.
How adoptive T-cell therapy works
Isolation of patient T cells.
Selection of an appropriate TCR for a particular indication.
- The TCR is introduced into the patient T cells using a vector system.
- Modified T cells (TCR-Ts) are expanded to large numbers in 10-15 days.
TCR-T cells are reinfused into the patient.
Billions of TCR-T cells induce a targeted immune response of combatting large tumor burdens.
Structure and function of T cell receptors
T cells are distinguished from other lymphocytes (types of white blood cells) by the presence of T cell receptors (TCRs) on the cell surface. TCRs allow T cells to identify cancer targets, e.g. tumor-specific antigens presented on the surface of the tumor cells. TCRs are multi-protein complexes composed of several invariant CD3 elements (these elements are important for the expression of and signalling by the TCR at the cell surface and without them the TCR cannot locate to the surface of the T cell or transmit the activation signal to the nucleus) and two different chains, a TCR-alpha chain (“α”) and a TCR-beta chain ( “β”). Each TCR chain has a variable (V) region linked to a constant (C) region. Together, the paired Vα and Vβ regions provide a single antigen-binding site. The paired variable regions of the TCR represent a well-defined structure on the surface of T cells, which determines TCR specificity and contributes to the entire repertoire of antigen specific T cells. The TCR on a T cell recognizes complexes of peptide plus HLA (human leucocyte antigen), a type of cell surface protein that helps the immune system distinguish the body’s own healthy cells from diseased pathogen-infected or tumor cells.
Medigene’s TCR-T pipeline
Medigene is developing a pipeline of TCRs that could potentially be used in future TCR-Ts as therapeutic drug candidates for the treatment of patients with different types of tumors. These represent TCRs that recognize a variety of different tumor-associated antigens that could be used in different T cell subsets of patients. High numbers of TCR-T cells could be infused back into the patient, where they could seek and destroy the tumor cells now recognized by the newly added TCR.