Engineered aptimer targets malignant and tumor-associated T cells
The transcription factor STAT3 mediates tumor survival, proliferation, invasion, and immunosuppression, and is persistently activated in tumor cells and tumor-associated immune cells.
In T cells, STAT3 activation impairs anti-tumor responses, while inhibition or loss of STAT3 promotes anti-tumor responses.
In this issue of the Journal of Clinical Investigation, Hua Yu and colleagues at the Beckman Research Institute developed an aptamer-based strategy to deliver STAT3 siRNA and inhibit STAT3 in tumor cells and tumor-associated immune cells.
An aptamer that binds the cell surface receptor cytotoxic T lymphocyte-associated antigen-4 (CTLA), an inhibitor of the T cell anti-tumor response, was attached to STAT3 siRNA (CTLA4apt-STAT3 siRNA), allowing for targeted delivery to tumor-associated T cells, Tregs or malignant T cells.
Local or systemic administration of CTLA4apt STAT3 siRNA in different murine tumor models decreased STAT3 expression in CTLA4-expressing T cells, reduced tumor-associated Tregs, and decreased tumor growth and metastasis.
Importantly, CTLA4apt STAT3 siRNA inhibited tumor growth and promoted tumor cell apoptosis in mice bearing human T cell lymphoma.