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

Purpose gamma 9 delta 2 T lymphocytes have been shown to be directly cytotoxic against renal carcinoma cells. Lymphocytes T gamma delta 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 gamma delta (TM), an autologous cell-therapy product based on gamma 9 delta 2 T lymphocytes, in patients with mRCC. Experimental design A 1-h intravenous infusion of gamma 9 delta 2 T lymphocytes was administered alone during treatment cycle 1 and combined with a low dose of subcutaneous interleukin-2 (IL-2, 2 MIU/m(2) from Day 1 to Day 7) in the two subsequent cycles (at 3-week intervals). The dose of gamma 9 delta 2 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 gamma 9 delta 2 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. Conclusion The data collected in ten patients with mRCC indicate that repeated infusions of Innacell gamma delta (TM) 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 gamma delta (TM) for the treatment of cancers.