title: Phase-I study of Innacell gammadelta, an autologous cell-therapy product highly enriched in gamma9delta2 T lymphocytes, in combination with IL-2, in patients with metastatic renal cell carcinoma.
abstract: OBJECTIVE
  gamma9delta2 T lymphocytes have been shown to be directly cytotoxic against renal carcinoma cells. Lymphocytes T gammadelta can be selectively expanded in vivo with BrHPP (IPH1101, Phosphostim) and interleukin 2 (IL-2). A phase I Study was conducted in patients with metastatic renal cell carcinoma (mRCC) to determine the maximum-tolerated dose and safety of Innacell gammadelta, an autologous cell-therapy product based on gamma9delta2 T lymphocytes, in patients with mRCC.
  
  
  METHODS
  A 1-h intravenous infusion of gamma9delta2 T lymphocytes was administered alone during treatment cycle 1 and combined with a low dose of subcutaneous interleukin-2 (IL-2, 2 MIU/m2 from Day 1 to Day 7) in the two subsequent cycles (at 3-week intervals). The dose of gamma9delta2 T lymphocytes was escalated from 1 up to 8 x 10(9) cells.
  
  
  RESULTS
  Ten patients underwent a total of 27 treatment cycles. Immunomonitoring data demonstrate that gamma9delta2 T lymphocytes are initially cleared from the blood to reappear at the end of IL-2 administration. Dose-limiting toxicity occurred in one patient at the dose of 8 x 10(9) cells (disseminated intravascular coagulation). Other treatment-related adverse events (AEs) included mainly gastrointestinal disorders and flu-like symptoms (fatigue, pyrexia, rigors). Hypotension and tachycardia also occurred, especially with co-administered IL-2. Six patients showed stabilized disease. Time to progression was 25.7 weeks.
  
  
  CONCLUSIONS
  The data collected in ten patients with mRCC indicate that repeated infusions of Innacell gammadelta at different dose levels (up to 8 x 10(9) total cells), either alone or with IL-2 is well tolerated. These results are in favor of the therapeutic value of cell therapy with Innacell gammadelta for the treatment of cancers.
authors.affiliation: Department of Medical Oncology, Centre René Gauducheau, Nantes-Saint-Herblain, France. j-bennouna@nantes.fnclcc.fr
authors.forename: Jaafar
authors.initials: J
authors.lastname: Bennouna
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Bompas
authors.forename: Eve Marie
authors.initials: EM
authors.lastname: Neidhardt
authors.forename: Frédéric
authors.initials: F
authors.lastname: Rolland
authors.forename: Irène
authors.initials: I
authors.lastname: Philip
authors.forename: Céline
authors.initials: C
authors.lastname: Galéa
authors.forename: Samuel
authors.initials: S
authors.lastname: Salot
authors.forename: Soraya
authors.initials: S
authors.lastname: Saiagh
authors.forename: Marie
authors.initials: M
authors.lastname: Audrain
authors.forename: Marie
authors.initials: M
authors.lastname: Rimbert
authors.forename: Sylvie
authors.initials: S
authors.lastname: Lafaye-de Micheaux
authors.forename: Jérôme
authors.initials: J
authors.lastname: Tiollier
authors.forename: Sylvie
authors.initials: S
authors.lastname: Négrier
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D003131:Combined Modality Therapy; D018450:Disease Progression; D005260:Female; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D018655:Lymphocyte Count; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D011379:Prognosis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000970:Antineoplastic Agents; D007376:Interleukin-2; D016692:Receptors, Antigen, T-Cell, gamma-delta