PMID- 21068778
OWN - NLM
STAT- MEDLINE
DCOM- 20110708
LR  - 20171116
IS  - 1476-5462 (Electronic)
IS  - 0969-7128 (Linking)
VI  - 18
IP  - 4
DP  - 2011 Apr
TI  - Allogeneic gene-modified tumor cells (RCC-26/IL-7/CD80) as a vaccine in patients 
      with metastatic renal cell cancer: a clinical phase-I study.
PG  - 354-63
LID - 10.1038/gt.2010.143 [doi]
AB  - Despite novel targeted agents, prognosis of metastatic renal cell cancer (RCC) 
      remains poor, and experimental therapeutic strategies are warranted. Transfection 
      of tumor cells with co-stimulatory molecules and/or cytokines is able to increase 
      immunogenicity. Therefore, in our clinical study, 10 human leukocyte antigen 
      (HLA)-A(*)0201(+) patients with histologically-confirmed progressive metastatic 
      clear cell RCC were immunized repetitively over 22 weeks with 2.5-40 x 10(6) 
      interleukin (IL)-7/CD80 cotransfected allogeneic HLA-A(*)0201(+) tumor cells 
      (RCC26/IL-7/CD80). Endpoints of the study were feasibility, safety, immunological 
      and clinical responses. Vaccination was feasible and safe. In all, 50% of the 
      patients showed stable disease throughout the study; the median time to 
      progression was 18 weeks. However, vaccination with allogeneic RCC26/IL-7/CD80 
      tumor cells was not able to induce TH1-polarized immune responses. A TH2 cytokine 
      profile with increasing amounts of antigen-specific IL-10 secretion was observed 
      in most of the responding patients. Interferon-gamma secretion by patient lymphocytes 
      upon antigen-specific and non-specific stimulation was substantially impaired, 
      both before and during vaccination, as compared with healthy controls. This is 
      possibly due to profound tumor-induced immunosuppression, which may prevent 
      induction of antitumor immune responses by the gene-modified vaccine. Vaccination 
      in minimal residual disease with concurrent depletion of regulatory cells might 
      be one strategy to overcome this limitation.
FAU - Westermann, J
AU  - Westermann J
AD  - Department of Hematology, Oncology and Tumor Immunology, Charite-University 
      Medicine Berlin, Campus Virchow-Klinikum and Campus Berlin-Buch, Berlin, Germany. 
      joerg.westermann@charite.de
FAU - Florcken, A
AU  - Florcken A
FAU - Willimsky, G
AU  - Willimsky G
FAU - van Lessen, A
AU  - van Lessen A
FAU - Kopp, J
AU  - Kopp J
FAU - Takvorian, A
AU  - Takvorian A
FAU - Johrens, K
AU  - Johrens K
FAU - Lukowsky, A
AU  - Lukowsky A
FAU - Schonemann, C
AU  - Schonemann C
FAU - Sawitzki, B
AU  - Sawitzki B
FAU - Pohla, H
AU  - Pohla H
FAU - Frank, R
AU  - Frank R
FAU - Dorken, B
AU  - Dorken B
FAU - Schendel, D J
AU  - Schendel DJ
FAU - Blankenstein, T
AU  - Blankenstein T
FAU - Pezzutto, A
AU  - Pezzutto A
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101111
PL  - England
TA  - Gene Ther
JT  - Gene therapy
JID - 9421525
RN  - 0 (B7-1 Antigen)
RN  - 0 (Cancer Vaccines)
RN  - 0 (HLA Antigens)
RN  - 0 (Interleukin-7)
SB  - IM
MH  - Adult
MH  - Aged
MH  - B7-1 Antigen/metabolism
MH  - Cancer Vaccines/administration & dosage/*therapeutic use
MH  - Carcinoma, Renal Cell/*therapy
MH  - Cell Line, Tumor
MH  - Female
MH  - HLA Antigens/analysis
MH  - Humans
MH  - Interleukin-7/*immunology
MH  - Kidney Neoplasms/*therapy
MH  - Male
MH  - Middle Aged
MH  - T-Lymphocytes/immunology
MH  - Transfection
EDAT- 2010/11/12 06:00
MHDA- 2011/07/09 06:00
CRDT- 2010/11/12 06:00
PHST- 2010/11/12 06:00 [entrez]
PHST- 2010/11/12 06:00 [pubmed]
PHST- 2011/07/09 06:00 [medline]
AID - gt2010143 [pii]
AID - 10.1038/gt.2010.143 [doi]
PST - ppublish
SO  - Gene Ther. 2011 Apr;18(4):354-63. doi: 10.1038/gt.2010.143. Epub 2010 Nov 11.