Phase-I Study of Innacell Gammadelta, an Autologous Cell-Therapy Product Highly Enriched in gamma9delta2 T Lymphocytes, in Combination With IL-2, in Patients With Metastatic Renal Cell Carcinoma

Cancer Immunol Immunother. 2008 Nov;57(11):1599-609. doi: 10.1007/s00262-008-0491-8. Epub 2008 Feb 27.

Abstract

Purpose: gamma9delta2 T lymphocytes have been shown to be directly cytotoxic against renal carcinoma cells. Lymphocytes T gammadelta 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 gammadelta, an autologous cell-therapy product based on gamma9delta2 T lymphocytes, in patients with mRCC.

Experimental design: A 1-h intravenous infusion of gamma9delta2 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 gamma9delta2 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 gamma9delta2 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 gammadelta 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 gammadelta for the treatment of cancers.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Renal Cell / immunology
  • Carcinoma, Renal Cell / secondary
  • Carcinoma, Renal Cell / therapy*
  • Combined Modality Therapy
  • Disease Progression
  • Female
  • Humans
  • Immunotherapy*
  • Interleukin-2 / therapeutic use*
  • Kidney Neoplasms / immunology
  • Kidney Neoplasms / pathology
  • Kidney Neoplasms / therapy*
  • Lymphocyte Count
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Prognosis
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • Survival Rate
  • T-Lymphocytes / immunology*

Substances

  • Antineoplastic Agents
  • Interleukin-2
  • Receptors, Antigen, T-Cell, gamma-delta