Allogeneic Platform
Allogeneic Platform
AvenCell is developing allogeneic, switchable CAR-T cell products that are engineered to overcome the limitations of current gene-edited allogeneic T cell therapies.
Autologous T cell therapies require manufacturing of individualized cell products, which has a high logistical and financial burden and also requires several weeks to manufacture. In contrast, allogeneic T cell therapies manufactured from healthy donors overcome these bottlenecks:
- Allogeneic T cell products are readily available “off-the-shelf.”
- Manufacturing costs per dose are significantly lower for allogeneic T cell products as compared to autologous products.
- T cells from healthy donors are likely more effective in fighting cancer than immune cells gained from patients with a long disease history or who have undergone multiple cycles of therapy.
However, several immunological challenges must be overcome to provide a safe and persistent cell product with durable efficacy:
- Graft-versus-host disease (GvHD) – the attack of the patient’s body by the donor T cells – is a major safety concern. T cell receptors (TCR) expressed by the donor T cells are the key driver of GvHD.
- T cells from the patient can recognize allogeneic T cells as “non-self” or “foreign” and initiate the immune defense machinery to eliminate the donor T cells, particularly if these express mismatched HLA proteins. Removal of HLA molecules from the allogeneic donor cell surface can avoid rejection by host T cells.
- Allogeneic T cells lacking HLA class I are recognized by the patient’s natural killer cells (NKs) and rapidly eliminated.
In conclusion, both host T cell and NK cell mediated immune rejection can lead to limited persistence of donor T cells and thus have a negative impact on their therapeutic efficacy. Avoidance of rejection by drug-induced host immune suppression is only temporary and promotes the risk of infections.
AvenCell is leveraging Intellia Therapeutics Inc.’s proprietary allogeneic platform based on CRISPR/Cas9 technology to overcome these challenges. AvenCell has been granted a license to combine Intellia’s CRISPR/Cas9 allogeneic platform with AvenCell’s universal, switchable CAR T-cell platforms. The in-licensed approach applies a novel combination of edits to generate allogeneic T cell products with durable persistence in hosts leading to superior anti-tumor efficacy.
- Knock-out (KO) of TCR prevents GvHD.
- KO of HLA class II expression in combination with KO of an HLA Class I protein aim to create allogeneic T cells capable of escaping from recognition by host T and NK cells.
This unique combination enables AvenCell to achieve long-term durability and persistence of its engineered T cells allowing for greater therapeutic efficacy.
