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)
  • Soluble TCR Technology (sTCR)

    T cell receptors are natively expressed as transmembrane proteins recognizing peptide antigens in the context of HLA molecules. However, TCRs can also be expressed and produced in soluble forms (sTCR). sTCR technology can be used for cancer treatment by targeting various effector molecules to the tumour site or for diagnostic purposes in combination with sensitive imaging technologies.

    Soluble TCR Technology (sTCR)