Targeted T-Cell Therapy for Metastatic Pancreatic Cancer: A Case Report

Cell-based immunotherapy, in which autologous T cells are engineered to express receptors targeting cancer-based antigens, is an established treatment for hematologic cancers. Recent studies are expanding these therapies to treat solid tumor malignances.

Investigators from the National Cancer Institute report the case of a patient with pancreatic cancer metastasized to the lungs bearing a KRAS G12D mutation, in which autologous T-cells were engineered to express two allogeneic HLA-restricted KRAS G12D-reactive T-cell receptors. The patient had previously received perioperative FOLFIRINOX, underwent surgical resection of the primary tumor followed by chemoradiotherapy, and developed bilateral lung nodules. She also had received autologous tumor-infiltrating lymphocyte therapy. Prior to treatment with autologous engineered KRAS G12D-reactive T cells, she received tocilizumab followed by preconditioning cyclophosphamide; after T cell infusion she received high-dose IL-2 treatment.

Toxicities, including nausea, fever, hypotension, and myelosuppression, were manageable. One month after treatment the patient had a documented partial response in lung metastases (regression of 62%) which was maintained at 6 months. The authors report a second patient with pancreatic cancer with mutant KRAS G12D with liver and lung metastases who achieved a transient response to similar therapy at one month and died from the disease at 6 months.