PMID- 20371691
OWN - NLM
STAT- MEDLINE
DCOM- 20100812
LR  - 20210103
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Linking)
VI  - 16
IP  - 8
DP  - 2010 Apr 15
TI  - T-cell receptor gene-modified T cells with shared renal cell carcinoma 
      specificity for adoptive T-cell therapy.
PG  - 2333-43
LID - 10.1158/1078-0432.CCR-09-2897 [doi]
AB  - PURPOSE: Adoptive therapy with genetically engineered T cells carrying redirected 
      antigen specificity is a new option for the treatment of cancer. This approach is 
      not yet available for metastatic renal cell carcinoma (RCC), due to the scarcity 
      of therapeutically useful reagents. We analyzed tumor-infiltrating lymphocytes 
      (TIL) from RCC to identify T-cell specificities with shared tumor-specific 
      recognition to develop T-cell receptor (TCR)-engineered T lymphocytes for 
      adoptive therapy of RCC. EXPERIMENTAL DESIGN: We established a T-cell clone from 
      TIL that recognized a human leukocyte antigen (HLA)-A2-restricted tumor antigen. 
      The TCR alpha- and beta-chain genes were isolated, modified by codon optimization 
      and murinization, and retrovirally transduced into peripheral blood lymphocytes 
      (PBL). A TCR-expressing indicator line (B3Z-TCR53) was established to screen for 
      antigen prevalence in RCC, other malignancies, and normal cell counterparts. 
      RESULTS: TCR53-engineered PBL recapitulated the specificity of the TIL and showed 
      tumor-specific HLA-A2-restricted effector activities (IFN-gamma, tumor necrosis 
      factor-alpha, interleukin-2, macrophage inflammatory protein-1beta, 
      cytotoxicity). PBL-TCR53 of healthy donors and RCC patients exhibited similar 
      transduction efficiency, expansion, and polyfunctional profile. Using B3Z-TCR53 
      cells, 130 tumor and normal cells were screened and shared TCR53 peptide: MHC 
      expression was found in >60% of RCC and 25% of tumor lines of other histology, 
      whereas normal tissue cells were not recognized. CONCLUSIONS: To date, TCR53 is 
      the only TCR with shared HLA-A2-restricted recognition of RCC. It fulfills the 
      criteria for utilization in TCR gene therapy and advances T cell-based 
      immunotherapy to patients with RCC and other malignancies expressing the TCR 
      ligand.
FAU - Leisegang, Matthias
AU  - Leisegang M
AD  - Max-Delbruck-Center for Molecular Medicine, Berlin, Germany.
FAU - Turqueti-Neves, Adriana
AU  - Turqueti-Neves A
FAU - Engels, Boris
AU  - Engels B
FAU - Blankenstein, Thomas
AU  - Blankenstein T
FAU - Schendel, Dolores J
AU  - Schendel DJ
FAU - Uckert, Wolfgang
AU  - Uckert W
FAU - Noessner, Elfriede
AU  - Noessner E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100406
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (Receptors, Antigen, T-Cell, alpha-beta)
SB  - IM
MH  - Carcinoma, Renal Cell/genetics/immunology/*therapy
MH  - Cells, Cultured
MH  - Cytotoxicity, Immunologic/immunology
MH  - Flow Cytometry
MH  - HLA-A2 Antigen/genetics/immunology
MH  - Humans
MH  - *Immunotherapy, Adoptive
MH  - Kidney/cytology/metabolism
MH  - Kidney Neoplasms/genetics/immunology/*therapy
MH  - Lymphocytes, Tumor-Infiltrating/*immunology
MH  - Receptors, Antigen, T-Cell, alpha-beta/*genetics
MH  - T-Cell Antigen Receptor Specificity
MH  - T-Lymphocytes/immunology/metabolism/*transplantation
EDAT- 2010/04/08 06:00
MHDA- 2010/08/13 06:00
CRDT- 2010/04/08 06:00
PHST- 2010/04/08 06:00 [entrez]
PHST- 2010/04/08 06:00 [pubmed]
PHST- 2010/08/13 06:00 [medline]
AID - 1078-0432.CCR-09-2897 [pii]
AID - 10.1158/1078-0432.CCR-09-2897 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2010 Apr 15;16(8):2333-43. doi: 10.1158/1078-0432.CCR-09-2897. 
      Epub 2010 Apr 6.