Original Article

Cancer Immunology, Immunotherapy

, Volume 57, Issue 11, pp 1599-1609

First online:

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

  • Jaafar BennounaAffiliated withDepartment of Medical Oncology, Centre René GauducheauCentre René Gauducheau Email author 
  • , Emmanuelle BompasAffiliated withDepartment of Medical Oncology, Centre René Gauducheau
  • , Eve Marie NeidhardtAffiliated withDepartment of Medical Oncology, Centre Léon Bérard
  • , Frédéric RollandAffiliated withDepartment of Medical Oncology, Centre René Gauducheau
  • , Irène PhilipAffiliated withDepartment of Medical Oncology, Centre Léon Bérard
  • , Céline GaléaAffiliated withInnate Pharma SAS
  • , Samuel SalotAffiliated withInnate Pharma SAS
  • , Soraya SaiaghAffiliated withUTCG and Immunomonitoring Laboratory, Hôtel-Dieu Hospital
  • , Marie AudrainAffiliated withUTCG and Immunomonitoring Laboratory, Hôtel-Dieu Hospital
    • , Marie RimbertAffiliated withUTCG and Immunomonitoring Laboratory, Hôtel-Dieu Hospital
    • , Sylvie Lafaye-de MicheauxAffiliated withInnate Pharma SAS
    • , Jérôme TiollierAffiliated withInnate Pharma SAS
    • , Sylvie NégrierAffiliated withDepartment of Medical Oncology, Centre Léon Bérard

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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 carcinoma γ9δ2 T lymphocytes Interleukin-2 Clinical efficacy Safety and tolerability