Adoptive T-Cell Transfer to Treat Lymphangioleiomyomatosis. Journal Article

Authors: Han, F; Dellacecca, ER; Barse, LW; Cosgrove, C; Henning, SW; Ankney, CM; Jaishankar, D; Yemelyanov, A; Krymskaya, VP; Dilling, DF; Le Poole, IC
Article Title: Adoptive T-Cell Transfer to Treat Lymphangioleiomyomatosis.
Abstract: 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 kidney tumor cells from aged 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 , 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 . 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.
Journal Title: American journal of respiratory cell and molecular biology
Publisher: Unknown  
Date Published: 2020