Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• European journal of cancer (1990), 2022-07, Vol.169, p.20-31

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2022

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. 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. 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). Allogeneic tumour lysate-DC treatment is feasible, safe and induces immune reactivity to PDAC expressed antigens. •Pancreatic cancer is an immune-deserted tumour and responses to immunotherapy are rare.•Allogeneic-tumour lysate-dendritic cell vaccination is feasible and safe in patients with pancreatic cancer.•Dendritic cell vaccination was immunogenic and demonstrated T-cell activation after therapy.•Therapy-induced cross-reactive T-cell responses against autologous tumour were found.