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 Aerts; C H J van Eijck

doi:10.1016/j.ejca.2022.03.015

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

Eur J Cancer. 2022 Jul:169:20-31. doi: 10.1016/j.ejca.2022.03.015. Epub 2022 Apr 28.

Authors

S P Lau¹, L Klaase², M Vink², J Dumas³, K Bezemer⁴, A van Krimpen², R van der Breggen⁵, L V Wismans⁶, M Doukas⁷, W de Koning⁸, A P Stubbs⁹, D A M Mustafa³, H Vroman², R Stadhouders¹⁰, J B Nunes⁵, C Stingl¹¹, N F C C de Miranda⁵, T M Luider¹¹, S H van der Burg¹², J G Aerts¹³, C H J van Eijck¹⁴

Affiliations

¹ Department of Surgery, Erasmus University Medical Center, 'S-Gravendijkwal 230, 3015CE, Rotterdam, the Netherlands; Department of Pulmonary Medicine, Erasmus University Medical Center, 'S-Gravendijkwal 230, 3015CE, Rotterdam, the Netherlands.
² Department of Pulmonary Medicine, Erasmus University Medical Center, 'S-Gravendijkwal 230, 3015CE, Rotterdam, the Netherlands.
³ Department of Pathology, The Tumor Immuno-Pathology Laboratory, Erasmus University Medical Center, 'S-Gravendijkwal 230, 3015CE, Rotterdam, the Netherlands.
⁴ Department of Pulmonary Medicine, Erasmus University Medical Center, 'S-Gravendijkwal 230, 3015CE, Rotterdam, the Netherlands; Amphera B.V., Onderwijsboulevard 225, 5223DE, 'S-Hertogenbosch, the Netherlands.
⁵ Department of Pathology, Leiden University Medical Center, P.O. Box 9600, 2300RC, Leiden, the Netherlands.
⁶ Department of Surgery, Erasmus University Medical Center, 'S-Gravendijkwal 230, 3015CE, Rotterdam, the Netherlands.
⁷ Department of Pathology, Erasmus University Medical Center, 'S-Gravendijkwal 230, 3015CE, Rotterdam, the Netherlands.
⁸ Department of Pathology, The Tumor Immuno-Pathology Laboratory, Erasmus University Medical Center, 'S-Gravendijkwal 230, 3015CE, Rotterdam, the Netherlands; Department of Pathology, Clinical Bioinformatics Unit, Erasmus University Medical Center, 'S-Gravendijkwal 230, 3015CE, Rotterdam, the Netherlands.
⁹ Department of Pathology, Clinical Bioinformatics Unit, Erasmus University Medical Center, 'S-Gravendijkwal 230, 3015CE, Rotterdam, the Netherlands.
¹⁰ Department of Pulmonary Medicine, Erasmus University Medical Center, 'S-Gravendijkwal 230, 3015CE, Rotterdam, the Netherlands; Department of Cell Biology, Erasmus University Medical Center, 'S-Gravendijkwal 230, 3015CE, Rotterdam, the Netherlands.
¹¹ Department of Neurology, Clinical and Cancer Proteomics, Erasmus University Medical Center, 'S-Gravendijkwal 230, 3015CE, Rotterdam, the Netherlands.
¹² Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, P.O. Box 9600, 2300RC, Leiden, the Netherlands.
¹³ Department of Pulmonary Medicine, Erasmus University Medical Center, 'S-Gravendijkwal 230, 3015CE, Rotterdam, the Netherlands; Erasmus MC Cancer Institute, Erasmus University Medical Center, 'S-Gravendijkwal 230, 3015CE, Rotterdam, the Netherlands.
¹⁴ Department of Surgery, Erasmus University Medical Center, 'S-Gravendijkwal 230, 3015CE, Rotterdam, the Netherlands. Electronic address: [email protected].

PMID: 35490565
DOI: 10.1016/j.ejca.2022.03.015

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.

Keywords: Dendritic cell; Immunotherapy; Pancreatic cancer; T cell.

Publication types

Clinical Trial, Phase I

MeSH terms

Antigens, Neoplasm
Cancer Vaccines* / adverse effects
Dendritic Cells
Hematopoietic Stem Cell Transplantation*
Humans
Immunotherapy / adverse effects
Neoplasm Recurrence, Local / drug therapy
Pancreatic Neoplasms* / drug therapy
T-Lymphocytes

Substances

Antigens, Neoplasm
Cancer Vaccines