Neoantigen T-cell receptor gene therapy in metastatic pancreatic ductal adenocarcinoma

A patient with progressive metastatic pancreatic cancer was treated with a single infusion of 16.2 x 10⁹ autologous T cells that had been genetically engineered to clonally express two allogeneic HLA-C*08:02-restricted T-cell receptors (TCR) targeting mutant KRAS G12D expressed by the tumors. The patient had regression of visceral metastases (overall partial response of 75%. The response was ongoing at 6 months. Engineered T cells constituted more than 2% of all the circulating peripheral-blood T cells 6 months after the cell transfer. The authors conclude that in this patient, TCR gene therapy targeting the KRAS G12D driver mutation mediated the objective regression of metastatic pancreatic cancer (quick take video summary).