RESUMEN
Pancreatic cancer remains one of the most difficult cancers to treat; very few effective therapies are available, with surgery being the sole chance for cure-yet surgery is not a viable option for most pancreatic cancer patients. Immunotherapy has the potential to provide a non-cross-resistant mechanism of antitumor activity that can be integrated with surgery, radiation therapy, and chemotherapy. However, the inherent instability of the tumorgenome as well as tumor tolerance mechanisms are significant practical obstacles that must be overcome if immune-based approaches for pancreatic cancer can achieve its promise. Recent advances in both tumor immunology and vaccine design have already resulted in promising preliminary data from phase I studies, and additional trials are already in progress. This article summarizes some of the progress and challenges in immunotherapy research.
Asunto(s)
Inmunoterapia/métodos , Neoplasias Pancreáticas/terapia , Antígeno B7-1 , Vacunas contra el Cáncer/inmunología , Vacunas contra el Cáncer/uso terapéutico , Predicción , Humanos , Tolerancia Inmunológica , Inmunidad Celular , Inmunoterapia/clasificación , Páncreas/inmunología , Neoplasias Pancreáticas/inmunología , Miembro 7 de la Superfamilia de Receptores de Factores de Necrosis TumoralRESUMEN
PURPOSE: Allogeneic granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting tumor vaccines can cure established tumors in the mouse, but their efficacy against human tumors is uncertain. We have developed a novel GM-CSF-secreting pancreatic tumor vaccine. To determine its safety and ability to induce antitumor immune responses, we conducted a phase I trial in patients with surgically resected adenocarcinoma of the pancreas. PATIENTS AND METHODS: Fourteen patients with stage 1, 2, or 3 pancreatic adenocarcinoma were enrolled. Eight weeks after pancreaticoduodenectomy, three patients received 1 x 10(7) vaccine cells, three patients received 5 x 10(7) vaccine cells, three patients received 10 x 10(7) vaccine cells, and five patients received 50 x 10(7) vaccine cells. Twelve of 14 patients then went on to receive a 6-month course of adjuvant radiation and chemotherapy. One month after completing adjuvant treatment, six patients still in remission received up to three additional monthly vaccinations with the same vaccine dose that they had received originally. RESULTS: No dose-limiting toxicities were encountered. Vaccination induced increased delayed-type hypersensitivity (DTH) responses to autologous tumor cells in three patients who had received >or= 10 x 10(7) vaccine cells. These three patients also seemed to have had an increased disease-free survival time, remaining disease-free at least 25 months after diagnosis. CONCLUSION: Allogeneic GM-CSF-secreting tumor vaccines are safe in patients with pancreatic adenocarcinoma. This vaccine approach seems to induce dose-dependent systemic antitumor immunity as measured by increased postvaccination DTH responses against autologous tumors. Further clinical evaluation of this approach in patients with pancreatic cancer is warranted.