Autologous dendritic cells pulsed with allogeneic tumour cell lysate induce tumour-reactive T-cell responses in patients with pancreatic cancer: A phase I study

S. P. Lau, L. Klaase, M. Vink, J. Dumas, K. Bezemer, A. van Krimpen, R. van der Breggen, L. V. Wismans, M. Doukas, W. de Koning, A. P. Stubbs, D. A.M. Mustafa, H. Vroman, R. Stadhouders, J. B. Nunes, C. Stingl, N. F.C.C. de Miranda, T. M. Luider, S. H. van der Burg, J. G. AertsC. H.J. van Eijck*

*Corresponding author for this work

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Abstract

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.

Original languageEnglish
Pages (from-to)20-31
Number of pages12
JournalEuropean Journal of Cancer
Volume169
DOIs
Publication statusPublished - 1 Jul 2022

Bibliographical note

Funding 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].

Funding 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].

Publisher Copyright:
© 2022 The Author(s)

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