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Published on: September 23, 2021
Tumor-Adhesive Chitosan-Derived Multi-Immune Agonist Unleashes Strong and Durable Anti-Cancer Immunity
Huilan He1,2, Liang Liu1,2,3, Yun Zheng1,2
1College of Pharmaceutical Sciences and State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, 215123, China.
Abstract:
The immunomodulation of the tumor microenvironment is critical for effective cancer immunotherapy, particularly for tumors that exhibit limited responses to conventional treatments. However, current immune agonists developed for tumor immunomodulation face several challenges, such as poor intratumoral retention, inadequate biocompatibility, and restricted cellular targets, which ultimately hamper their therapeutic efficacy and clinical application. In this study, a tumor-adhesive chitosan-tethered immune agonist construct (TACTIC) is introduced, which demonstrates good biocompatibility and robust immunostimulatory effects, enhancing the immunogenicity of tumor cells while simultaneously stimulating pro-inflammatory responses in various immune cell populations. Mechanistic investigations reveal that TACTIC targets multiple signaling pathways, conferring it to effectively remodel the irradiated tumor microenvironment, improve tumor control on murine cancer models post-radiotherapy, and elicit systemic immune responses with memory effects. The findings highlight the potential of TACTIC as a powerful macromolecular immune adjuvant, paving the way for its broader application in innovative cancer immunotherapies.
Insights
A novel chitosan-tethered immune agonist construct (TACTIC) enhances anti-tumor immunity by improving the tumor microenvironment and stimulating immune cells. This approach shows promise for improving cancer immunotherapy outcomes.
Area of Science:
- Biomedical Engineering
- Cancer Immunology
- Drug Delivery Systems
Background:
- Effective cancer immunotherapy relies on modulating the tumor microenvironment.
- Current immune agonists face challenges like poor retention and biocompatibility, limiting efficacy.
- Tumors with limited response to conventional treatments require novel immunomodulatory strategies.
Purpose of the Study:
- To develop and evaluate a tumor-adhesive chitosan-tethered immune agonist construct (TACTIC).
- To assess TACTIC's biocompatibility, immunostimulatory effects, and ability to enhance tumor immunogenicity.
- To investigate TACTIC's potential in remodeling the tumor microenvironment and improving cancer immunotherapy.
Main Methods:
- Development of a chitosan-tethered immune agonist construct (TACTIC).
- Evaluation of TACTIC's biocompatibility and immunostimulatory effects in vitro.
- Assessment of TACTIC's efficacy in murine cancer models post-radiotherapy, including mechanistic investigations.
- Analysis of systemic immune responses and memory effects.
Main Results:
- TACTIC demonstrated good biocompatibility and robust immunostimulatory effects.
- The construct enhanced tumor cell immunogenicity and stimulated pro-inflammatory responses.
- TACTIC effectively remodeled the irradiated tumor microenvironment and improved tumor control in vivo.
- Systemic immune responses with memory effects were elicited.
Conclusions:
- TACTIC shows significant potential as a macromolecular immune adjuvant for cancer immunotherapy.
- The construct effectively overcomes limitations of current immune agonists.
- TACTIC offers a promising strategy for innovative cancer treatments, particularly post-radiotherapy.
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