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 (TCR-Ts). TCR-Ts for any selected tumor antigen 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-T platform, TCR-Ts with selected specificities are isolated and characterized and subsequently assessed to potentially treat various types of blood cancers and solid tumors.
- Isolated TCR-Ts are of natural origin and are chosen to have optimal affinities and hence the TCR-Ts do not need mutational engineering to improve their capacity to find and bind tumor cells.
- The TCR-T platform can deliver TCR-Ts recognizing a variety of different tumor antigens, representing either common antigens shared by tumors or patient-individual neoantigens.
- TCR-Ts for both CD4+ and CD8+ T cells can be generated, which recognize peptide fragments presented by different MHC class I and MHC class II alleles, providing greater potential to for effective treatments to larger numbers of patients.
How adoptive T-cell therapy works
- The TCR-T is introduced into the patient T cells using a vector system.
- Modified T cells are expanded to large numbers in 10-15 days.
Structure and function of T cell receptors
T cells are distinguished from other lymphocytes by the presence of T cell receptors (TCRs) on the cell surface. TCRs allow T cells to identify cancer targets, e.g. tumor-targeted antigens presented on the surface of the tumor cells. Each T cell receptor is a heterodimeric protein complex composed of one TCR α chain and one TCR β chain. The TCR heterodimers consist of a variable and a constant region. The polypeptide chains are linked together. Each variable region provides a single antigen-binding site. The TCR is associated with a CD3 complex, which combines three transmembrane signaling molecules. TCRs recognize a peptide fragment of a TAA presented by a major histocompatibility complex (MHC) molecule on the target cell. The activation of the T cell to kill the cancer cell starts upon simultaneous binding of a T cell co-receptor complex (CD4+ or CD8+ complex with CD3) to activate the T cell.
Medigene’s TCR-T pipeline
Medigene’s TCR-T pipeline is being built to contain a collection of TCR-Ts that recognize different antigens which are expressed by various types of tumor. Upon completion, Medigene’s TCR-T pipeline will enable individuals of diverse patient populations to be matched for the treatment with TCR-Ts according to their MHC molecules and specificities for antigens expressed by tumor cells. The pipeline is built by natural TCR-Ts with optimal affinities that can be expressed in CD4+ or CD8+ cells, selected by their specificities. Peptide fragments presented by different MHC molecules (both MHC class I and class II allotypes) can be targeted by TCR-Ts to treat different types of tumor.