T cells play a key role in cell-mediated immunity and can mediate long-lived, antigen-specific effector and immune memory responses. They detect their target cells through T cell receptors (TCR) on their surface. The TCR is a transmembrane complex that mediates antigen-specific activation of T cells. It recognizes foreign peptide antigens presented on major histocompatibility complex (MHC) molecules on the surface of target cells.
CD8 T cells recognize peptides derived from the inside of the target cells in the context of MHC class I molecules. In contrast, CD4 T cells recognize peptides derived from extracellular antigens in the context of MHC class II molecules on antigen presenting cells (APCs).
Traditionally the focus has been on CD8 T cells as they can directly kill target cells, recent studies however showed the key role of CD4 T cells in obtaining a broad, efficient and sustained anti-tumour immune response.
Zelluna has a broad portfolio of TCRs derived from both CD4 and CD8 T cell clones.
Our TCRs are unique in the sense that they have been isolated from patients showing remarkable long-term clinical responses in vaccine trials. The TCRs have been tailored by the immune system of these long-term survivors and have already shown clinical benefit. Furthermore, they have been exposed to peptide epitopes from the entire human proteome for years without showing any off-tumour reactivity.
Our TCRs currently under development are directed against a TGFβRII frameshift mutation and the universal cancer antigens hTERT and RAS and can be used in the treatment of a wide range of cancer types.