In healthy individuals, T cells identify and kill infected or abnormal cells, including cancer cells. Cell-based immuno‐oncology treatments, such as CAR-T, seek to harness the power of the body’s immune system to target and kill cancer: re-arming T cells with “seek and destroy” capacity. There are two distinct technologies that can be used to arm T cells – CARs and TCRs:
- CAR (Chimeric antigen receptor): CARs are engineered Ab molecules with activation signals that, when present at the surface of T‐cells, enable them to recognize specific proteins or antigens that are present on the surface of other cells (e.g. cancer cells) and become activated to kill that cell.
- TCR (T cell receptor) – this utilises the T cells’ own receptor (TCR) for a specific antigen: The TCR for a particular specificity can be a naturally occurring T cell or the genes encoding a particular TCR (e.g. a TCR specific for a cancer (protein) antigen) can be inserted into another T cell, enabling it to better recognize cancer cells.
CAR-T cells harness the exquisite specificity of mAbs for tumour antigens and link this to the cell killing power of cytotoxic T cells to create a new type of T cell; one that is not constrained to identify tumour cells via the TCR only. This creates a pre-activated type of T cell capable of recognising a broader range of targets, thus adding a new dimension to the immune system repertoire.
Cartherics uses both CAR and TCR specificities to provide enhanced tumour cell recognition and their destruction – a dual specificity that, combined with other antigen enhancements, forms the basis of Cartherics’ “GoldiLox™” products.
Cartherics’ plan is to effect genetic enhancement of cytotoxic killer T cells to have dual cancer binding receptors – their own natural TCR plus CAR-T technology to seek out tumour cells, enhanced further with a docking antibody. These cells are multiplied and can be transfused alone or with other drugs that increase the immunotherapeutic response [e.g. by uncoupling of immune handbrakes (checkpoint blockade inhibitors) or suppressing Tregs], so that they will be extremely effective in destroying cancers including solid tumours.
Cartherics has filed provisional patent applications on its technologies and has established strategically important links with other leading commercial and academic groups who have complementary technology to develop cutting-edge products. Cartherics will thus create and access a portfolio of state-of-the-art IP to support delivery of next generation CAR-T technology.
Cartherics intends to apply stem cell technology to these engineered immune cells to generate an endless supply of cancer killing T cells for both the initial treatment of patients, as well as follow-up treatment in the event of relapse. Cartherics will utilise stem cell lines derived from rare homozygous HLA haplotype donors, which are compatible with the most common HLA types in the Western and Asian communities. These cells will be engineered to express CAR constructs and then differentiated into T cells (CAR-T), co-expressing an endogenous T cell receptor to cancer peptides.
Most immunotherapy companies use one approach or the other (TCR or CAR-T); Cartherics combines both technologies to provide maximum potential cancer killing (“dual targeting”).
Cartherics’ approach provides the T cell with a specific dual targeting mechanism, thereby enhancing its ability to seek, identify, interact with and destroy tumour cells bearing either selected antigen.