Tough target.

This case report describes an exciting (although n=1) response to T-cell receptor gene therapy in a patient with refractory, metastatic pancreatic cancer. The group had previously identified tumor infiltrating T-cells targeting KRAS G12D in a patient with colorectal cancer. They were able to achieve tumor regression in that patient by treatment with autologous KRAS G12D T-cells. KRAS G12D is also frequently mutated in pancreatic cancer. So, a patient with KRAS G12D mutated pancreatic cancer was treated with a single infusion of CAR T-cells targeting KRAS G12D along with high dose interleukin-2. The patient experienced a robust partial response (per RECIST) of 72% that was ongoing at 6 months. An important limitation is that the the T-cell receptors are restricted to HLA-C*08:02, which is expressed by only 8% of White and 11% of Black persons. | Leidner, N Engl J Med 2022