Lymph node-biomimetic scaffold boosts CAR-T therapy against solid tumor.

Area of Science:

• Biomedical Engineering
• Immunotherapy
• Materials Science

Background:

• Chimeric antigen receptor (CAR)-T cell therapy shows promise but faces challenges in solid tumors due to limited T-cell infiltration and persistence.
• Current CAR-T cell delivery methods often fail to adequately support T-cell activation and expansion within the tumor microenvironment.

Purpose of the Study:

• To develop and evaluate a novel three-dimensional biomimetic scaffold for enhanced CAR-T cell loading, delivery, activation, and expansion.
• To improve the therapeutic efficacy of CAR-T cells against solid tumors through a biomimetic scaffold-based approach.

Main Methods:

• A porous poly(lactic-co-glycolic acid) scaffold was fabricated using microfluidics.
• The scaffold was modified with T-cell stimulatory signals (anti-CD3, anti-CD28 antibodies) and cytokines.
• CAR-T cell expansion and persistence were assessed in vitro and in vivo using a cervical tumor model.

Main Results:

• The scaffold demonstrated significant CAR-T cell expansion, achieving 50-fold expansion in vitro and 15-fold expansion in vivo.
• Sustained CAR-T cell expansion for up to 30 days was observed within the tumor model.
• The scaffold-mediated CAR-T cell therapy significantly inhibited tumor growth.

Conclusions:

• The developed biomimetic scaffold effectively supports CAR-T cell expansion and persistence, overcoming key limitations in solid tumor treatment.
• This versatile platform offers a promising strategy for enhancing CAR-T cell delivery and activation, paving the way for improved immunotherapies against solid tumors.