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Researchers have found promising early evidence that an enzyme called DNase I could help boost the effectiveness of CAR T cell therapy in treating certain solid cancers. In preclinical experiments presented by Dr. Alexey Stepanov of The Scripps Research Institute at the Society for Immunotherapy of Cancer (SITC) Spring Scientific 2025 Cell Therapy Meeting, DNase I was shown to enhance the immune response against metastatic melanoma in mice when used alongside CAR T cells. The findings were part of research led by Xenetic Biosciences, a company developing immuno-oncology treatments for hard-to-treat cancers.
The study tested the combination in a mouse model of lung metastasis using aggressive melanoma cells. A single injection of DNase I with CAR T cells significantly reduced the number of metastatic tumours and improved survival compared to CAR T cells alone. DNase I appeared to work by breaking down neutrophil extracellular traps (NETs)—web-like structures produced by immune cells that can suppress T cell activity in the tumour microenvironment.
Further analysis showed that DNase I helped lower the expression of "exhaustion" markers on T cells, suggesting it helped reinvigorate the immune response. While DNase I alone didn’t prolong survival, it showed real potential when paired with immunotherapy.
Xenetic is now advancing this approach toward clinical trials, particularly for difficult cancers like pancreatic and colorectal cancer. If successful, this could lead to more effective treatments by enhancing the power of CAR T cells against solid tumors, which have so far proven challenging to treat.
