Background: Pancreatic ductal adenocarcinoma (PDAC) is notorious for its poor prognosis even after curative resection. Responses to immunotherapy are rare and related to inadequate T-cell priming. We previously demonstrated the potency of allogeneic lysate-dendritic cell (DC) vaccination in a preclinical model. Here we translate this concept to patients. Methods: In this phase I study, patients with resected PDAC were included when they demonstrated no radiologic signs of recurrence after standard-of-care treatment. Allogeneic tumour lysate-loaded autologous monocyte-derived DCs were injected at weeks 0, 2, 4 and at months 3 and 6. Objectives are feasibility, safety and immunogenicity of allogeneic tumour-DCs. The presence of tumour antigens shared between the vaccine and patient tumours was investigated. Immunological analyses were performed on peripheral blood, skin and tumour. Results: Ten patients were included. DC production and administration were successful. All patients experienced a grade 1 injection-site and infusion-related reaction. Two patients experienced a grade 2 fever and 1 patient experienced a grade 3 dyspnoea. No vaccine-related serious adverse events were observed. Shared tumour antigens were found between the vaccine and patient tumours. All evaluated patients displayed a vaccine-induced response indicated by increased frequencies of Ki67+ and activated PD-1+ circulating T-cells. In addition, treatment-induced T-cell reactivity to autologous tumour of study patients was detected. Seven out of ten patients have not experienced disease recurrence or progression at a median follow-up of 25 months (15–32 months). Conclusion: Allogeneic tumour lysate-DC treatment is feasible, safe and induces immune reactivity to PDAC expressed antigens.
Bibliographical noteFunding Information:
This work was supported by the Survival with Pancreatic Cancer Foundation [grant number OVIT17-06]; and the Health?Holland TKI Life Sciences & Health [grant number LSHM16046]; and the European Research Council (ERC) under the European Union's Horizon 2020 Research and Innovation Program [grant number 852832 to N.F.C.C.d.M].
This work was supported by the Survival with Pancreatic Cancer Foundation [grant number OVIT17-06 ]; and the Health∼Holland TKI Life Sciences & Health [grant number LSHM16046 ]; and the European Research Council (ERC) under the European Union's Horizon 2020 Research and Innovation Program [grant number 852832 to N.F.C.C.d.M].
© 2022 The Author(s)