Publication date: Oct 08, 2024

Intratumorally injection of CAR-T cells to treat melanoma can reduce the incidence of systemic side effects and ensure an adequate concentration of CAR-T cells. However, few targeting ligands and hostile tumor microenvironment (TME) inhibit the CAR-T cells’ survival and infiltration. An in situ hyaluronic acid-manganese-capsaicin complex nanogel (HA-Mn-CAP Gel) was designed by forming complex nanogel based on the main skeleton material of hyaluronic acid (HA). It targeted CD44 and TRPV receptors through HA and CAP, concentrated and released Mn at melanoma, subsequently relieving the hypoxia in the tumor and increasing the expression of CAR-T cells’ specific ligands. Cell experiments showed that HA-Mn-CAP Gel significantly enhanced the expression of representative NKGD ligands (MICA/B and ULBP) >2. 7 times on A375 melanoma cells. Sequential administration of HA-Mn-CAP Gel and NKGD/CAR-T increased the tumor inhibition rate about 1. 5 times that of the NKGD/CAR-T group in melanoma-bearing NSG mice. The results of immunohistochemistry and immunofluorescence assays showed that the combined HA-Mn-CAP Gel and NKGD/CAR-T significantly increased the proliferation and infiltration of T cells, especially for CD8 cells. Therefore, the new promising strategy of increasing the target ligand expression and adjusting TME before administering CAR-T cells is suitable for treating solid tumors.

Semantics

Original Article