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

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. © 2008 Springer-Verlag.