Act local: Mice data point to potential of delivering checkpoint inhibitor depots direct to tumors

Systemically delivered checkpoint inhibitors have grown into the cornerstone of immuno-oncology. Now, a team at the Terasaki Institute for Biomedical Innovation in Los Angeles wants to improve the effects of the molecules through local delivery.

Writing in ACS Applied Materials & Interfaces, the team describes the loading of anti-PD-1 checkpoint inhibitors in shear-thinning biomaterials made of gelatin and silicate nanoplatelets. Upon injection into the melanoma tumors of mice, the formulation formed a gel depot, significantly reduced cancer growth and increased the level of CD8-positive T cells in peripheral blood.

The injections also increased the level of tumor-infiltrating CD4-positive helper T cells, CD8-positive cytotoxic T cells and tumor death, offering early validation of the idea that local delivery can maximize therapeutic efficacies while reducing side effects. Helper T cells and T killer cells were up 44% and 36%, respectively, versus the negative controls. Tumor cell death increased by 13.2 times. 

“The results obtained here clearly demonstrate the effectiveness of targeted, controllable and sustainable antibody delivery to reinstate the body's natural defense mechanisms against cancer," Ali Khademhosseini, Ph.D., director and CEO at the Terasaki Institute, said in a statement. "Its potential in creating combination therapies further extends its impact."

Khademhosseini and his collaborators created an injectable gelatin biomaterial containing disc-shaped silicate nanoplatelets with charged surfaces to optimize binding to the checkpoint inhibitors. Delivery to the tumors was performed using a minimally invasive injection.

The team looked at the factors that affected the release of the checkpoint inhibitor, revealing that the percentage of silicate nanoplatelets and pH influence the release of the drug molecules. The findings point to ways to tune the release of the checkpoint inhibitor.