This new therapeutic approach in the treatment of HCC could be very important as without treatment the 5 year survival rate is just 5%. Globally, HCC accounts for 746,000 deaths, and in the UK alone is responsible for over 4,000 deaths per year.
Glypican-3 (GPC3) is a tumour associated antigen expressed in up to 70% of HCC but not in healthy human tissue. Isolating GPC3-specific T-cell receptors and expressing them on patient’s T-cells can help treat HCC, as these T cells can recognise and eliminate GPC3-postive HCC.
The study detected and expanded MHC-multimer-positive CD8+ T-cells specific for targeted GPC3 epitopes and grew T-cell clones. From these clones, the most specific and active T-cell receptor was isolated. When this T-cell receptor was expressed on donor T cells it conferred specificity for GPC3, the HCC-associated antigen. Thus, it enables HLA-A2+ patient’s T cells to specifically kill GPC3+ HCC.
Systemic treatments for advanced stage HCC are constantly evolving and current approaches include drug treatment with sorafenib – yet the current standard of care still does not offer a strong enough prognosis for patients. Liver transplant is an option for only 10 -15% of HCC carriers diagnosed at an early stage and therefore the importance of other treatment options for patients is critical. This is a treatment gap that adoptive T-cell therapy could potentially fill.