T cells play an essential role in cell-mediated immunity by participating in defending human bodies against foreign pathogens or autologous tumor cells via recognizing specific antigens. Compared to traditional antibodies, the most prominent feature of T-cell receptors are their abilities to target internal tumor antigens presented by MHC molecules. As a result, their therapeutic value is much greater. By integrating a panel of advanced technologies, Axis is able to re-engineer T cell receptors to effectively clear cancer cells.
The essence of cell immunotherapy is to stimulate a patient’s own anti-cancer immune cells, such as T cells. As a result, the patient's immune response to tumor burdens can be boosted and tumor proliferation can be significantly inhibited. Other benefits may include mild side effects and low recurrence rates. This therapy may work for all cancer stages.
Axis is committed to developing genetically modified T cells with enhanced affinity and specificity for tumor antigens to achieve better efficacy without severe side effects. The technology platform encompasses target identification, T cell cloning, TCR optimization, T cell modification and T cell amplification.
Cancer cells in the body can be identified by targets, or antigens, presented on the cell surface or inside the cell.
The majority of cancer cell antigens derive from intracellular proteins, while the remaining are surface associated targets on the membrane or secreted.
While conventional CAR-T are restricted to surface associated targets, TCR-T are capable of recognizing peptide antigens derived from intracellular proteins.
Intracellular proteins are a rich source of potential tumor-specific antigenic targets.
When intracellular proteins are broken down in the cancer cell, the resulting peptide antigens attach to MHCs (major histocompatibility complex), which are then expressed on the cell surface.
T-cell receptors (TCR) on T-cells will be able to recognize and attach to the tumor-specific peptide antigens presented on MHCs, triggering tumor killing response.
1. High binding affinity and specificity
In a normal environment, the threshold for T-cells to trigger a tumor killing response is determined by the number of activating ligands, or TCR clusters (receptor attached to antigen).
The greater the number of TCR clusters, the greater the chance of triggering attack against the tumor and the lower the chance of tolerance.
Our technology has increased the binding affinity of TCRs to an optimal level that lowers the trigger threshold while reducing off-target, or non-specific, activity in redirected cancer cell killing.
2. High expression level and persistence
Our TCRs have shown to have excellent expression level on engineered T cells and persistence in patients, which will enable anti-tumor immune activity in patients for longer periods of time.
3. Broad patient coverage
MHCs in humans are also known as HLA (Human Leukocyte Antigen) complex, which help the immune system to distinguish the proteins made by foreign objects in a patients body.
HLA genes produce proteins that present on the cell surface, that bind to peptides (protein fragments) that are produced from within the cell. MHCs display these peptides to the body’s immune system.
HLA genes can have many variations and literature has shown that variations can differ by [nationality and ethnicity], which are recognized differently by T cells.
Our world-class TCR-T technology enables us to develop unique High Affinity TCR-T candidates that can target different variations of HLA genes, to address the needs of more cancer patients more effectively.