PMID- 18301889
OWN - NLM
STAT- MEDLINE
DCOM- 20081118
LR  - 20240426
IS  - 0340-7004 (Print)
IS  - 1432-0851 (Electronic)
IS  - 0340-7004 (Linking)
VI  - 57
IP  - 11
DP  - 2008 Nov
TI  - 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.
PG  - 1599-609
LID - 10.1007/s00262-008-0491-8 [doi]
AB  - 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.
FAU - Bennouna, Jaafar
AU  - Bennouna J
AD  - Department of Medical Oncology, Centre Rene Gauducheau, Nantes-Saint-Herblain, 
      France. j-bennouna@nantes.fnclcc.fr
FAU - Bompas, Emmanuelle
AU  - Bompas E
FAU - Neidhardt, Eve Marie
AU  - Neidhardt EM
FAU - Rolland, Frederic
AU  - Rolland F
FAU - Philip, Irene
AU  - Philip I
FAU - Galea, Celine
AU  - Galea C
FAU - Salot, Samuel
AU  - Salot S
FAU - Saiagh, Soraya
AU  - Saiagh S
FAU - Audrain, Marie
AU  - Audrain M
FAU - Rimbert, Marie
AU  - Rimbert M
FAU - Lafaye-de Micheaux, Sylvie
AU  - Lafaye-de Micheaux S
FAU - Tiollier, Jerome
AU  - Tiollier J
FAU - Negrier, Sylvie
AU  - Negrier S
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080227
PL  - Germany
TA  - Cancer Immunol Immunother
JT  - Cancer immunology, immunotherapy : CII
JID - 8605732
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Interleukin-2)
RN  - 0 (Receptors, Antigen, T-Cell, gamma-delta)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Agents/*therapeutic use
MH  - Carcinoma, Renal Cell/immunology/secondary/*therapy
MH  - Combined Modality Therapy
MH  - Disease Progression
MH  - Female
MH  - Humans
MH  - *Immunotherapy
MH  - Interleukin-2/*therapeutic use
MH  - Kidney Neoplasms/immunology/pathology/*therapy
MH  - Lymphocyte Count
MH  - Lymphocytes, Tumor-Infiltrating/immunology/pathology
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Prognosis
MH  - Receptors, Antigen, T-Cell, gamma-delta/*immunology
MH  - Survival Rate
MH  - T-Lymphocytes/*immunology
PMC - PMC11030608
COIS- Consultancy Agreement: Jaafar Bennounax. Clinical Investigator: Emmanuelle 
      Bompas, Eve Marie Neidhardt, Frederic Rolland, Irene Philip, Sylvie Negrier. 
      Innate Pharma personnel: Celine Galea, Samuel Salot, Sylvie Lafaye-de Micheaux, 
      Jerome Tiollier.
EDAT- 2008/02/28 09:00
MHDA- 2008/11/19 09:00
PMCR- 2008/02/27
CRDT- 2008/02/28 09:00
PHST- 2007/08/31 00:00 [received]
PHST- 2008/02/13 00:00 [accepted]
PHST- 2008/02/28 09:00 [pubmed]
PHST- 2008/11/19 09:00 [medline]
PHST- 2008/02/28 09:00 [entrez]
PHST- 2008/02/27 00:00 [pmc-release]
AID - 491 [pii]
AID - 10.1007/s00262-008-0491-8 [doi]
PST - ppublish
SO  - Cancer Immunol Immunother. 2008 Nov;57(11):1599-609. doi: 
      10.1007/s00262-008-0491-8. Epub 2008 Feb 27.