Retargeting NK92 cells using an HLA-A2-restricted, EBNA3C-specific chimeric antigen receptor Journal Article
| Authors: | Tassev, D. V.; Cheng, M.; Cheung, N. K. |
| Article Title: | Retargeting NK92 cells using an HLA-A2-restricted, EBNA3C-specific chimeric antigen receptor |
| Abstract: | 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. © 2012 Nature America, Inc. All rights reserved. |
| Keywords: | controlled study; nonhuman; antigen expression; t lymphocyte; animal cell; animals; cell line; cytotoxicity; hybrid protein; epitope; adoptive transfer; killer cells, natural; antibodies; epitopes, t-lymphocyte; oligopeptides; lymphocyte antigen receptor; receptors, antigen; epstein barr virus; single chain fragment variable antibody; phage display; antibody dependent cellular cytotoxicity; virus protein; hla a2 antigen; hla-a2 antigen; cho cells; cricetinae; human herpesvirus 4; immunoglobulin fragments; antigens, viral; chimerism; scfv; immunoglobulin fc fragment; chimeric antigen receptors; hla-a2; nk92mi; scfv-fc |
| Journal Title: | Cancer Gene Therapy |
| Volume: | 19 |
| Issue: | 2 |
| ISSN: | 0929-1903 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2012-02-01 |
| Start Page: | 84 |
| End Page: | 100 |
| Language: | English |
| DOI: | 10.1038/cgt.2011.66 |
| PROVIDER: | scopus |
| PUBMED: | 21979579 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 March 2012" - "CODEN: CGTHE" - "Source: Scopus" |
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