title: Massive expansion of regulatory T-cells following interleukin 2 treatment during a phase I-II dendritic cell-based immunotherapy of metastatic renal cancer.
abstract: 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.
authors.affiliation: Department of Biotherapies, Bâtiment CERVI, 83 Boulevard de L'Hôpital, Paris Cedex, France. francois.lemoine@upmc.fr
authors.forename: François M
authors.initials: FM
authors.lastname: Lemoine
authors.forename: Mustapha
authors.initials: M
authors.lastname: Cherai
authors.forename: Camille
authors.initials: C
authors.lastname: Giverne
authors.forename: Dalia
authors.initials: D
authors.lastname: Dimitri
authors.forename: Michelle
authors.initials: M
authors.lastname: Rosenzwajg
authors.forename: Helene
authors.initials: H
authors.lastname: Trebeden-Negre
authors.forename: Nathalie
authors.initials: N
authors.lastname: Chaput
authors.forename: Benoit
authors.initials: B
authors.lastname: Barrou
authors.forename: Nicolas
authors.initials: N
authors.lastname: Thioun
authors.forename: Bernard
authors.initials: B
authors.lastname: Gattegnio
authors.forename: Frederic
authors.initials: F
authors.lastname: Selles
authors.forename: Alain
authors.initials: A
authors.lastname: Six
authors.forename: Nabih
authors.initials: N
authors.lastname: Azar
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Lotz
authors.forename: Agnes
authors.initials: A
authors.lastname: Buzyn
authors.forename: Mathilde
authors.initials: M
authors.lastname: Sibony
authors.forename: Annick
authors.initials: A
authors.lastname: Delcourt
authors.forename: Olivier
authors.initials: O
authors.lastname: Boyer
authors.forename: Serge
authors.initials: S
authors.lastname: Herson
authors.forename: David
authors.initials: D
authors.lastname: Klatzmann
authors.forename: Roger
authors.initials: R
authors.lastname: Lacave
mesh_terms: D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000628:therapy*; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007167:Immunotherapy / Q000379:methods; D007376:Interleukin-2 / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000276:immunology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*
chemical_list: D018952:Antigens, CD34; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D007376:Interleukin-2