Cancer Immunology, Immunotherapy

, Volume 59, Issue 10, pp 1521–1530

Phase I study of bromohydrin pyrophosphate (BrHPP, IPH 1101), a Vγ9Vδ2 T lymphocyte agonist in patients with solid tumors

  • Jaafar Bennouna
  • Vincent Levy
  • Hélène Sicard
  • Hélène Senellart
  • Marie Audrain
  • Sandrine Hiret
  • Frédéric Rolland
  • Heriberto Bruzzoni-Giovanelli
  • Marie Rimbert
  • Céline Galéa
  • Jérome Tiollier
  • Fabien Calvo
Original Article

DOI: 10.1007/s00262-010-0879-0

Cite this article as:
Bennouna, J., Levy, V., Sicard, H. et al. Cancer Immunol Immunother (2010) 59: 1521. doi:10.1007/s00262-010-0879-0
  • 235 Views

Abstract

Purpose

Vγ9Vδ2 (γδ) T lymphocytes, a critical peripheral blood lymphocyte subset, are directly cytotoxic against many solid and hematologic tumor types. Vγ9Vδ2 T lymphocytes can be selectively expanded in vivo with BrHPP (IPH1101) and IL-2. The present phase I trial was conducted with the aim of determining the maximum-tolerated dose (MTD) and safety of IPH1101 combined with a low dose of IL-2 in patients with solid tumors.

Experimental design

A 1-h intravenous infusion of IPH11 was administered alone at cycle 1, combined with a low dose of SC IL-2 (1 MIU/M2 d1 to d7) in the subsequent cycles (day 1 every 3 weeks). The dose of IPH1101 was escalated from 200 to 1,800 mg/m2.

Results

As much as 28 patients with solid tumors underwent a total of 109 treatment cycles. Pharmacodynamics data demonstrate that γδ T lymphocyte amplification in humans requires the co-administration of IL-2 and is dependent on IPH 1101 dose. Dose-limiting toxicity occurred in two patients at a dose of 1,800 mg/m2: one grade 3 fever (1 patient) and one grade 3 hypotension (1 patient) suggesting cytokine release syndrome immediately following the first infusion. At lower doses the treatment was well tolerated; the most frequent adverse events were mild fever, chills and abdominal pain, without exacerbation in the IL-2 combined cycles.

Conclusion

IPH1101 in combination with SC low-dose IL-2 is safe, well tolerated and induces a potent γδ T lymphocyte expansion in patients. Its clinical activity will be evaluated in phase II clinical trials.

Keywords

Bromohydrin pyrophosphateVγ9Vδ2 T lymphocytePhase I trialSolid tumors

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Jaafar Bennouna
    • 1
  • Vincent Levy
    • 2
  • Hélène Sicard
    • 3
  • Hélène Senellart
    • 1
  • Marie Audrain
    • 4
  • Sandrine Hiret
    • 1
  • Frédéric Rolland
    • 1
  • Heriberto Bruzzoni-Giovanelli
    • 2
  • Marie Rimbert
    • 4
  • Céline Galéa
    • 3
  • Jérome Tiollier
    • 3
  • Fabien Calvo
    • 2
  1. 1.Department of Medical OncologyCentre René GauducheauNantes-Saint-HerblainFrance
  2. 2.Clinical Investigation Center-INSERM, Saint-Louis HospitalParisFrance
  3. 3.Innate Pharma SASMarseilleFrance
  4. 4.UTCG and Immunomonitoring LaboratoryHôtel Dieu HospitalNantesFrance