Massive expansion of regulatory T-cells following interleukin 2 treatment during a phase I-II dendritic cell-based immunotherapy of metastatic renal cancer. - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue International Journal of Oncology Année : 2009

Massive expansion of regulatory T-cells following interleukin 2 treatment during a phase I-II dendritic cell-based immunotherapy of metastatic renal cancer.

Mustapha Cherai
  • Fonction : Auteur
Camille Giverne
  • Fonction : Auteur
Dalia Dimitri
  • Fonction : Auteur
Michelle Rosenzwajg
  • Fonction : Auteur
  • PersonId : 934586
Helene Trebeden-Negre
  • Fonction : Auteur
Benoit Barrou
  • Fonction : Auteur
Nicolas Thioun
  • Fonction : Auteur
Bernard Gattegnio
  • Fonction : Auteur
Frederic Selles
  • Fonction : Auteur
Nabih Azar
  • Fonction : Auteur
Jean Pierre Lotz
  • Fonction : Auteur
Agnes Buzyn
  • Fonction : Auteur
Annick Delcourt
  • Fonction : Auteur
Olivier Boyer
Serge Herson
  • Fonction : Auteur
David Klatzmann
Roger Lacave
  • Fonction : Auteur

Résumé

Cytotoxic chemotherapy is ineffective in metastatic renal cancer. However, systemic administration of interleukin 2 (IL-2) or infusion of dendritic cells (DCs) loaded with tumor extracts can lead to some response rates with concomitant survival improvements. We report the results of a phase I-II pilot study combining DCs and IL-2 where six patients were included. DCs were derived from bone marrow CD34+ cells and loaded with autologous tumor extracts. CD34-DC vaccines were infused subcutaneously at day 45, 52, 59, 90 and 120 following surgery in combination with IL-2, that was subsequently administrated after the 3rd and 4th DC vaccinations. Preparation of tumor extracts and CD34-DCs were satisfactory in all patients but one. Due to rapid tumor progression, one patient was excluded before vaccination. In the 4 remaining patients, two received 3 vaccinations, while the 2 others received 5 vaccinations and the full IL-2 treatment. No adverse effect due to the vaccinations was observed. A specific immune response against autologous tumor cells was observed in the 2 patients who completed the treatment. Interestingly, these 2 patients had a more prolonged survival than the patients receiving 3 vaccinations. Importantly, a transient and massive increase of circulating natural regulatory T-cells (nTregs) was evidenced in 3 patients following IL-2 administration. Overall, the use of CD34-DC vaccines is feasible, safe and non-toxic. A specific anti-tumor immune response can be detected. However, our data highlights that IL-2 is a potent inducer of nTregs in vivo and as such may have a negative impact on cancer immunotherapy.

Domaines

Immunothérapie
Fichier non déposé

Dates et versions

hal-00420217 , version 1 (28-09-2009)

Identifiants

Citer

François M Lemoine, Mustapha Cherai, Camille Giverne, Dalia Dimitri, Michelle Rosenzwajg, et al.. Massive expansion of regulatory T-cells following interleukin 2 treatment during a phase I-II dendritic cell-based immunotherapy of metastatic renal cancer.. International Journal of Oncology, 2009, 35 (3), pp.569-81. ⟨hal-00420217⟩
268 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More