| First Author | Zhang T | Year | 2012 |
| Journal | J Immunol | Volume | 189 |
| Issue | 5 | Pages | 2290-9 |
| PubMed ID | 22851709 | Mgi Jnum | J:189856 |
| Mgi Id | MGI:5447130 | Doi | 10.4049/jimmunol.1103495 |
| Citation | Zhang T, et al. (2012) An NKp30-based chimeric antigen receptor promotes T cell effector functions and antitumor efficacy in vivo. J Immunol 189(5):2290-9 |
| abstractText | NKp30 is a natural cytotoxicity receptor that is expressed on NK cells and recognizes B7-H6, which is expressed on several types of tumors but few normal cells. To target effector T cells against B7-H6+ tumors, we developed several chimeric AgRs (CARs) based on NKp30, which contain the CD28- and/or CD3zeta-signaling domains with the transmembrane domains from CD3zeta, CD28, or CD8alpha. The data show that chimeric NKp30-expressing T cells responded to B7-H6+ tumor cells. The NKp30 CAR-expressing T cells produced IFN-gamma and killed B7-H6 ligand-expressing tumor cells; this response was dependent upon ligand expression on target cells but not on MHC expression. PBMC-derived dendritic cells also express NKp30 ligands, including immature dendritic cells, and they can stimulate NKp30 CAR-bearing T cells to produce IFN-gamma, but to a lesser extent. The addition of a CD28-signaling domain significantly enhanced the activity of the NKp30 CAR in a PI3K-dependent manner. Adoptive transfer of T cells expressing a chimeric NKp30 receptor containing a CD28-signaling domain inhibited the growth of a B7-H6-expressing murine lymphoma (RMA/B7-H6) in vivo. Moreover, mice that remained tumor-free were resistant to a subsequent challenge with the wild-type RMA tumor cells, suggesting the generation of immunity against other tumor Ags. Overall, this study demonstrates the specificity and therapeutic potential of adoptive immunotherapy with NKp30 CAR-expressing T cells against B7-H6+ tumor cells in vivo. |
