Enhancing adoptive T-cell therapy with fucoidan-based IL-2 delivery microcapsules

Area of Science:

• Biotechnology
• Immunology
• Materials Science

Background:

• Adoptive cell therapy (ACT) shows promise for solid cancers, often enhanced by Interleukin-2 (IL-2).
• Clinical use of IL-2 with ACT is limited by short exposure times and significant toxicities.
• Developing localized delivery systems is crucial for improving IL-2 efficacy and safety in cancer immunotherapy.

Purpose of the Study:

• To design a complex coacervate system for sustained and protected intratumoral delivery of IL-2.
• To evaluate the efficacy of this delivery system in enhancing T-cell responses and anti-tumor activity.
• To assess the system's ability to overcome the challenges of IL-2 toxicity and short half-life.

Main Methods:

• A complex coacervate (FPC²) was formulated using fucoidan and poly-l-lysine to encapsulate IL-2.
• IL-2-loaded FPC² was embedded in a pH-modulating injectable gel (FPC²-IG) for intratumoral administration.
• The system's effects on T-cell expansion, tumor microenvironment, and anti-tumor efficacy were assessed in vivo.

Main Results:

• IL-2-loaded FPC² demonstrated preferential expansion of CD8+ T cells over regulatory T cells ex vivo.
• Intratumoral injection of FPC²-IG-IL-2 increased tumor-infiltrating cytotoxic lymphocytes and reduced myeloid populations.
• Localized T-cell activation and persistence were observed within the tumor, leading to effective tumor eradication by adoptively transferred T cells.

Conclusions:

• The FPC²-IG delivery system enables sustained, localized IL-2 delivery, enhancing ACT efficacy for solid tumors.
• This strategy mitigates IL-2 related toxicities by confining its action to the tumor site.
• The FPC²-IG system represents a promising platform for improving T-cell-based cancer immunotherapies.