Two major challenges facing
cancer immunotherapy are the relatively low therapeutic efficacy and the potential side effects. New drug delivery system and efficient
drug combination are required to overcome these challenges. We utilize an
alginate hydrogel system to locally deliver 2 FDA-approved drugs,
celecoxib and programmed death 1 (PD-1)
monoclonal antibody (mAb), to treat
tumor-bearing mice. In two
cancer models, B16-F10
melanoma and 4T1 metastatic
breast cancer, the
alginate hydrogel delivery system significantly improves the antitumor activities of
celecoxib (CXB), PD-1 mAb, or both combined. These effects are associated with the sustained high concentrations of the drugs in peripheral circulation and within
tumor regions. Strikingly, the simultaneous dual local delivery of
celecoxib and PD-1 from this
hydrogel system synergistically enhanced the presence of CD4+inteferon (IFN)-γ+ and CD8+IFN-γ+ T cells within the
tumor as well as in the immune system. These effects are accompanied with reduced CD4+FoxP3+ regulatory T cells (Tregs) and myeloid derived suppressor cells (MDSCs) in the
tumor, reflecting a weakened immuosuppressive response. Furthermore, this combinatorial
therapy increases the expression of two anti-angiogenic
chemokines C-X-C motif
ligand (CXCL) 9 and CXCL10, and suppresses the intratumoral production of
interleukin (IL)-1,
IL-6, and cycloxygenase-2 (COX2), suggesting a dampened pro-
tumor angiogenic and inflammatory microenvironment. This
alginate-
hydrogel-mediated, combinatorial
therapy of
celecoxib and PD-1 mAb provides a potential valuable regimen for treating human
cancer.