Technology

Scientific Platform

T cells can be both highly potent direct killers of tumour cells and central orchestrators of a broader anti-tumour immune response.

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.

  • Our TCRs have unique features:

    Our TCRs have unique features:

    • They were tailored by the patient’s own immune system
    • They are not engineered in any way
    • They have circulated in patients for years without showing on target/off tumour toxicity
    • They have already demonstrated clinical efficacy
    • They show strong avidity for their respective target
  • Zelluna is currently exploring the use of TCRs both in cellular and soluble formats.

  • Adoptive Cell Therapy (ACT)

    In Adoptive Cell Therapy (ACT), T cells are engineered to express a specific tumour targeting receptor – either a chimeric antigen receptor (CAR) or a T cell receptor (TCR) – that recognise and kill tumour cells in the body of the patient.

    The potential of this approach has been demonstrated in the successful use of genetically modified T cells in the treatment of B cell malignancies in clinical trials and holds promise of treating patients with advanced solid tumours.

    Adoptive Cell Therapy (ACT)