Cancer Immunology, Immunotherapy

, Volume 57, Issue 11, pp 1599–1609

Phase-I study of Innacell γδ™, an autologous cell-therapy product highly enriched in γ9δ2 T lymphocytes, in combination with IL-2, in patients with metastatic renal cell carcinoma

Authors

    • Department of Medical OncologyCentre René Gauducheau
    • Centre René Gauducheau
  • Emmanuelle Bompas
    • Department of Medical OncologyCentre René Gauducheau
  • Eve Marie Neidhardt
    • Department of Medical OncologyCentre Léon Bérard
  • Frédéric Rolland
    • Department of Medical OncologyCentre René Gauducheau
  • Irène Philip
    • Department of Medical OncologyCentre Léon Bérard
  • Céline Galéa
    • Innate Pharma SAS
  • Samuel Salot
    • Innate Pharma SAS
  • Soraya Saiagh
    • UTCG and Immunomonitoring LaboratoryHôtel-Dieu Hospital
  • Marie Audrain
    • UTCG and Immunomonitoring LaboratoryHôtel-Dieu Hospital
  • Marie Rimbert
    • UTCG and Immunomonitoring LaboratoryHôtel-Dieu Hospital
  • Sylvie Lafaye-de Micheaux
    • Innate Pharma SAS
  • Jérôme Tiollier
    • Innate Pharma SAS
  • Sylvie Négrier
    • Department of Medical OncologyCentre Léon Bérard
Original Article

DOI: 10.1007/s00262-008-0491-8

Cite this article as:
Bennouna, J., Bompas, E., Neidhardt, E.M. et al. Cancer Immunol Immunother (2008) 57: 1599. doi:10.1007/s00262-008-0491-8

Abstract

Purpose

γ9δ2 T lymphocytes have been shown to be directly cytotoxic against renal carcinoma cells. Lymphocytes T γδ 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 γδ™, an autologous cell-therapy product based on γ9δ2 T lymphocytes, in patients with mRCC.

Experimental design

A 1-h intravenous infusion of γ9δ2 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 γ9δ2 T lymphocytes was escalated from 1 up to 8 × 109 cells.

Results

Ten patients underwent a total of 27 treatment cycles. Immunomonitoring data demonstrate that γ9δ2 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 × 109 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.

Conclusion

The data collected in ten patients with mRCC indicate that repeated infusions of Innacell γδ™ at different dose levels (up to 8 × 109 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 γδ™ for the treatment of cancers.

Keywords

Metastatic renal cell carcinomaγ9δ2 T lymphocytesInterleukin-2Clinical efficacySafety and tolerability

Copyright information

© Springer-Verlag 2008