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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.
The response in metastatic pancreatic cancer to a targeted T-cell therapy is provocative, and further study of this technology is warranted. The case patient treated had a limited and arguably asymptomatic tumor burden with lung nodules. The expense and complexity of this treatment, as well as the likely need to target rare mutational subsets, will continue to qualify the movement of such therapies forward.
Leidner R et al.
Title: Neoantigen T-cell receptor gene therapy in pancreatic cancer.
Source: N Engl J Med 2022 Jun 2; [e-pub]. (Abstract/FREE Full Text)