New research highlights the promise of a novel stem cell treatment strategy for leptomeningeal brain metastasis (LBM), a severe form of metastatic brain cancer that spreads to membranes surrounding the brain and spinal cord and occurs in up to 20 percent of people with cancer.
The researchers say their findings in newly developed preclinical models of metastatic non-small cell lung cancer (NSCLC) support the pursuit of clinical trials for this treatment strategy.
LBM is a severe form of disease that often occurs in those diagnosed with NSCLC, breast cancer, and melanoma, and is linked to poor rates of survival, ranging from eight to 10 weeks.
While first-line therapies for cancer such as chemotherapy are ineffective in treating LBM, immune checkpoint inhibitors (ICIs) often have more success in treating NSCLC brain metastasis.
However, the efficacy of ICIs in treating LBM from NSCLC has been less successful.
Mass General Brigham scientists first created immune-competent LBM mouse models that mimic LBM inpatient settings to investigate this further.
To enhance tumour cell killing and modulate immune tumour environment, scientists explored testing the therapeutic activity of allogeneic dual stem cells releasing oncolytic herpes simplex virus (oHSV) and single chain variable fragment of anti-PD-1 (scFvPD-1) in the preclinical models.
Dual stem cells releasing oHSV and scFvPD-1 were delivered locally via intrathecal injection, a technique already used to treat other diseases.
Their findings showed that treatment with dual stem cells enhanced therapeutic outcomes by inducing immunogenic cell death, activating anti-tumour T cell signaling, and disrupting oxidative phosphorylation, making tumours sensitive to cisplatin.
Results are published in the Journal of the National Cancer Institute.
“Our results support that our dual stem cell-based immunotherapy delivered locally can ultimately improve clinical outcome in patients with NSCLC LBM,” said corresponding author Khalid Shah, MS, PhD, director of the Centre for Stem Cell and Translational Immunotherapy (CSTI) and the vice chair of research in the Department of Neurosurgery at Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system.
“Our work continues to build on developing new mechanism-based therapies for difficult-to-treat tumours in the brain.”
Source: Mass General Brigham
