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01.11.2008 | Original Article

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

verfasst von: Jaafar Bennouna, Emmanuelle Bompas, Eve Marie Neidhardt, Frédéric Rolland, Irène Philip, Céline Galéa, Samuel Salot, Soraya Saiagh, Marie Audrain, Marie Rimbert, Sylvie Lafaye-de Micheaux, Jérôme Tiollier, Sylvie Négrier

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 11/2008

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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.

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Titel: 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
verfasst von: Jaafar Bennouna
Emmanuelle Bompas
Eve Marie Neidhardt
Frédéric Rolland
Irène Philip
Céline Galéa
Samuel Salot
Soraya Saiagh
Marie Audrain
Marie Rimbert
Sylvie Lafaye-de Micheaux
Jérôme Tiollier
Sylvie Négrier
Publikationsdatum: 01.11.2008
Verlag: Springer-Verlag
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 11/2008
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-008-0491-8

Springer Medizin

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