| First Author | Han F | Year | 2020 |
| Journal | Am J Respir Cell Mol Biol | Volume | 62 |
| Issue | 6 | Pages | 793-804 |
| PubMed ID | 32078336 | Mgi Jnum | J:306071 |
| Mgi Id | MGI:6713216 | Doi | 10.1165/rcmb.2019-0117OC |
| Citation | Han F, et al. (2020) Adoptive T-Cell Transfer to Treat Lymphangioleiomyomatosis. Am J Respir Cell Mol Biol 62(6):793-804 |
| abstractText | Patients with lymphangioleiomyomatosis (LAM) develop pulmonary cysts associated with neoplastic, smooth muscle-like cells that feature neuroendocrine cell markers. The disease preferentially affects premenopausal women. Existing therapeutics do not cure LAM. As gp100 is a diagnostic marker expressed by LAM lesions, we proposed to target this immunogenic glycoprotein using TCR transgenic T cells. To reproduce the genetic mutations underlying LAM, we cultured Tsc2(-/-) kidney tumor cells from aged Tsc2 heterozygous mice and generated a stable gp100-expressing cell line by lentiviral transduction. T cells were isolated from major histocompatibility complex-matched TCR transgenic pmel-1 mice to measure cytotoxicity in vitro, and 80% cytotoxicity was observed within 48 hours. Antigen-specific cytotoxicity was likewise observed using pmel-1 TCR-transduced mouse T cells, suggesting that transgenic T cells may likewise be useful to treat LAM in vivo. On intravenous injection, slow-growing gp100(+) LAM-like cells formed lung nodules that were readily detectable in severe combined immunodeficient/beige mice. Adoptive transfer of gp100-reactive but not wild-type T cells into mice significantly shrunk established lung tumors, even in the absence of anti-PD-1 therapy. These results demonstrate the treatment potential of adoptively transferred T cells to eliminate pulmonary lesions in LAM. |
