Grooved Microneedle Patch Augments Adoptive T Cell Therapy Against Solid Tumors via Diverting Regulatory T Cells.
Adv Mater
; 36(30): e2401667, 2024 Jul.
Article
en En
| MEDLINE
| ID: mdl-38843541
ABSTRACT
The efficacy of adoptive T cell therapy (ACT) for the treatment of solid tumors remains challenging. In addition to the poor infiltration of effector T (Teff) cells limited by the physical barrier surrounding the solid tumor, another major obstacle is the extensive infiltration of regulatory T (Treg) cells, a major immunosuppressive immune cell subset, in the tumor microenvironment. Here, this work develops a grooved microneedle patch for augmenting ACT, aiming to simultaneously overcome physical and immunosuppressive barriers. The microneedles are engineered through an ice-templated method to generate the grooved structure for sufficient T-cell loading. In addition, with the surface modification of chemokine CCL22, the MNs could not only directly deliver tumor-specific T cells into solid tumors through physical penetration, but also specifically divert Treg cells from the tumor microenvironment to the surface of the microneedles via a cytokine concentration gradient, leading to an increase in the ratio of Teff cells/Treg cells in a mouse melanoma model. Consequently, this local delivery strategy of both T cell receptor T cells and chimeric antigen receptor T cells via the CCL22-modified grooved microneedles as a local niche could significantly enhance the antitumor efficacy and reduce the on-target off-tumor toxicity of ACT.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Inmunoterapia Adoptiva
/
Linfocitos T Reguladores
/
Agujas
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Adv Mater
Asunto de la revista:
BIOFISICA
/
QUIMICA
Año:
2024
Tipo del documento:
Article
País de afiliación:
China