Rapamycin Nanoparticles for the Treatment of Lymphangioleiomyomatosis

Lymphangioleiomyomatosis (LAM) is a rare, progressive lung disease primarily affecting women of childbearing age. Characterized by bi-allelic mutations in TSC1 or TSC2, LAM leads to elevated mTORC1 activity, resulting in pulmonary tumor nodules and reduced lung function. One possible method of treatment is the rapamycin drug which works through the inhibition of the mTOR. However, while rapamycin therapy slows tumor progression, it does not eliminate LAM cells, leaving lung transplantation as the only definitive treatment. To counter this, an innovative immunotherapy approach was tested through the application of nanoparticle rapamycin and the introduction of an antigen receptor (CAR). This was done through patient-derived xenograft (PDX) model, preserving the LAM microenvironment. These tissues were treated with rapamycin, nanoparticle rapamycin, or CAR CCR2 and then frozen into explants which were then sectioned for further analysis. These tissues were stained with different protein markers like gp100 and Ps6 and then imaged to quantify the effectiveness of each treatment. Immunotherapies show efficacy in PDX models as rapamycin models were 43% more effective than control. This work has broader implications for treating benign tumors and other rare diseases, ultimately striving for a curative, precision-based immunotherapy for LAM.