Related Experiment Video
Updated: May 28, 2026
08:48
Generating De Novo Antigen-specific Human T Cell Receptors by Retroviral Transduction of Centric Hemichain
Published on: October 25, 2016
Retargeting NK92 cells using an HLA-A2-restricted, EBNA3C-specific chimeric antigen receptor
D V Tassev1, M Cheng, N-K V Cheung
1Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Cancer Gene Therapy
|October 8, 2011
Summary
Researchers developed a novel chimeric antigen receptor (CAR) targeting Epstein-Barr virus peptides on cancer cells. This CAR effectively reprograms natural killer (NK) cells for potent cancer immunotherapy, offering a new avenue for treatment.
Area of Science:
- Immunology
- Cancer Research
- Molecular Biology
Background:
- Adoptive cell immunotherapy shows promise for cancer treatment.
- Targeting specific tumor antigens is crucial for effective immunotherapy.
- Single-chain variable fragments (scFvs) are valuable tools for antigen recognition.
Purpose of the Study:
- To isolate and characterize an scFv targeting an Epstein-Barr virus (EBV) peptide presented by HLA-A2.
- To engineer this scFv into a chimeric antigen receptor (CAR) for non-T cell reprogramming.
- To evaluate the efficacy of CAR-engineered NK cells against EBV-associated targets.
Main Methods:
- Isolation of scFvs using phage display panning against HLA-A2-peptide complexes.
- Characterization of scFv specificity, affinity, and functional activity (e.g., ADCC).
- Construction and expression of a CAR incorporating the scFv in NK92MI cells.
Main Results:
- An scFv (EBNA Clone 315) with high specificity for an EBNA3C-derived peptide on HLA-A2 was identified.
- The scFv, as a fusion protein, demonstrated detection sensitivity and induced ADCC.
- CAR-engineered NK92MI cells exhibited potent and specific cytotoxicity against the target T-cell epitope (TCE), exceeding scFv-Fc-mediated ADCC.
Conclusions:
- EBNA Clone 315 is a highly specific targeting moiety for an EBV-derived TCE.
- CAR technology can successfully reprogram NK cells to recognize specific TCEs.
- This study demonstrates a novel approach for developing cellular immunotherapies against EBV-associated malignancies.
