PMID- 21979579
OWN - NLM
STAT- MEDLINE
DCOM- 20120816
LR  - 20201215
IS  - 1476-5500 (Electronic)
IS  - 0929-1903 (Linking)
VI  - 19
IP  - 2
DP  - 2012 Feb
TI  - Retargeting NK92 cells using an HLA-A2-restricted, EBNA3C-specific chimeric 
      antigen receptor.
PG  - 84-100
LID - 10.1038/cgt.2011.66 [doi]
AB  - Advances in adoptive cell immunotherapy have led to several promising options for 
      cancer patients. Single-chain variable fragments (scFvs) were isolated from a 
      human phage display library by panning on recombinant human leukocyte antigen 
      (HLA)-A2-peptide complexes. A scFv (EBNA Clone 315) specific for HLA-A2 carrying 
      a 10 amino acid peptide (LLDFVRFMGV) derived from the Epstein-Barr virus latent 
      protein EBNA3C was fully characterized. EBNA Clone 315 displayed exquisite 
      specificity toward its targeted T-cell epitope (TCE) and did not cross-react with 
      the free peptide, HLA-A2 complexes, which carried irrelevant peptides, or 
      HLA-A2(-) cells. Furthermore, after engineering into a scFv-Fc fusion protein, we 
      were able to determine its affinity, detection sensitivity, and ability to induce 
      antibody-dependent cellular cytotoxicity (ADCC). As a proof-of-principle, a 
      chimeric antigen receptor (CAR) version of EBNA Clone 315 was used to reprogram 
      NK92MI cells. CAR-expressing NK92MI cells showed highly specific and potent 
      cytotoxicity toward the targeted TCE, with detection sensitivity of approximately 
      25 molecules and cytolytic capacity threefold greater than scFv-Fc-mediated ADCC. 
      For the first time, we show the successful reprogramming of non-T cells toward a 
      specific TCE using a CAR.
FAU - Tassev, D V
AU  - Tassev DV
AD  - Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY 
      10021, USA.
FAU - Cheng, M
AU  - Cheng M
FAU - Cheung, N-K V
AU  - Cheung NK
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111007
PL  - England
TA  - Cancer Gene Ther
JT  - Cancer gene therapy
JID - 9432230
RN  - 0 (Antigens, Viral)
RN  - 0 (EBNA-3C, epstein-barr virus)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Epstein-Barr Virus Nuclear Antigens)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (Immunoglobulin Fragments)
RN  - 0 (Oligopeptides)
RN  - 0 (Receptors, Antigen)
SB  - IM
MH  - Animals
MH  - Antigens, Viral/*immunology
MH  - CHO Cells
MH  - Cell Line
MH  - Chimerism
MH  - Cricetinae
MH  - Epitopes, T-Lymphocyte/immunology
MH  - Epstein-Barr Virus Nuclear Antigens
MH  - HLA-A2 Antigen/genetics/*immunology
MH  - Humans
MH  - Immunoglobulin Fragments/immunology
MH  - Killer Cells, Natural/*immunology
MH  - Oligopeptides/*immunology/metabolism
MH  - Receptors, Antigen/genetics/*immunology
EDAT- 2011/10/08 06:00
MHDA- 2012/08/17 06:00
CRDT- 2011/10/08 06:00
PHST- 2011/10/08 06:00 [entrez]
PHST- 2011/10/08 06:00 [pubmed]
PHST- 2012/08/17 06:00 [medline]
AID - cgt201166 [pii]
AID - 10.1038/cgt.2011.66 [doi]
PST - ppublish
SO  - Cancer Gene Ther. 2012 Feb;19(2):84-100. doi: 10.1038/cgt.2011.66. Epub 2011 Oct 
      7.