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:

1. 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.
2. 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.
3. 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.