| First Author | Bendle GM | Year | 2013 |
| Journal | J Immunol | Volume | 191 |
| Issue | 6 | Pages | 3232-9 |
| PubMed ID | 23940272 | Mgi Jnum | J:205767 |
| Mgi Id | MGI:5546434 | Doi | 10.4049/jimmunol.1301270 |
| Citation | Bendle GM, et al. (2013) Blockade of TGF-beta signaling greatly enhances the efficacy of TCR gene therapy of cancer. J Immunol 191(6):3232-9 |
| abstractText | TCR gene therapy is a promising approach for the treatment of various human malignancies. However, the tumoricidal activity of TCR-modified T cells may be limited by local immunosuppressive mechanisms within the tumor environment. In particular, many malignancies induce T cell suppression in their microenvironment by TGF-beta secretion. In this study, we evaluate whether blockade of TGF-beta signaling in TCR-modified T cells enhances TCR gene therapy efficacy in an autochthonous mouse tumor model. Treatment of mice with advanced prostate cancer with T cells genetically engineered to express a tumor-reactive TCR and a dominant-negative TGF-beta receptor II induces complete and sustained tumor regression, enhances survival, and leads to restored differentiation of prostate epithelium. These data demonstrate the potential to tailor the activity of TCR-modified T cells by additional genetic modification and provide a strong rationale for the clinical testing of TGF-beta signaling blockade to enhance TCR gene therapy against advanced cancers. |
