Researchers have developed an innovative injectable hydrogel to enhance neoadjuvant immunotherapy for triple-negative breast cancer (TNBC). This hydrogel combines the cyclin-dependent kinase 4/6 inhibitor Abemaciclib (Abe) with a peptide-NLG919 prodrug, forming nanofibers termed Abe-NF(g). Upon local injection, the hydrogel remains at the tumor site for at least seven days, serving as a reservoir that releases Abe and NLG919 directly into the tumor microenvironment. This localized delivery system significantly increases the concentration of therapeutic agents in the tumor while minimizing systemic exposure, thereby reducing potential side effects such as lymphopenia and hepatic toxicity.
The sustained release of Abe from the hydrogel induces immunogenic cell death, promotes dendritic cell maturation, and activates cytotoxic T lymphocytes (CTLs), all of which are crucial for an effective anti-tumor immune response. However, Abe can also upregulate indoleamine 2,3-dioxygenase 1 (IDO1), an enzyme that suppresses immune function. To counteract this, the co-delivered NLG919 within the hydrogel inhibits IDO1 activity, preventing the activation of regulatory T cells that could dampen the immune response. This dual-action approach not only enhances CTL infiltration into the tumor but also fosters the development of effector memory T cells, leading to a more robust and sustained inhibition of tumor growth. Click for More Details
