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Published on: May 2, 2025
Advanced biomaterials for the targeted delivery of immune checkpoint inhibitors to solid tumors
Emily M Henrich1, Kevin J McHugh2
1Department of Bioengineering, Rice University, USA.
Abstract:
Immune checkpoint inhibitors (ICIs) have revolutionized the way cancer is treated by engaging the patient's own immune system to attack cancer. ICIs can also achieve favorable outcomes in patients whose cancers are unresponsive or resistant to first-line therapies. Despite these exciting prospects, ICIs are ineffective in many patients and cause immune-related adverse events (irAEs) in up to 89 % of patients. Therefore, there is a clear clinical need to reduce irAEs while maintaining or improving the therapeutic efficacy of ICIs. The local administration of ICIs through intratumoral injection or peritumoral administration has been shown to increase the potency of these therapeutics while reducing irAEs and extending survival in preclinical models. However, the rapid systemic distribution of intratumorally delivered drugs (hours) prevents this strategy from achieving even better efficacy and reduced toxicity; this is particularly problematic for ICIs due to their long biological (weeks), consequently acting at non-target sites for weeks before being cleared by the body. Engineered biomaterials have the potential to enhance local administration by improving permeation and retention, employing antibody-mediated targeting, leveraging tumor microenvironment sense-and-respond systems, or taking advantage of cell trafficking. This paper reviews the cutting-edge delivery strategies shown to improve the safety and efficacy of drugs targeting PD-1, PD-L1, and CTLA-4 and identifies the most promising strategies for clinical translation.
Insights
Local delivery of immune checkpoint inhibitors (ICIs) using engineered biomaterials can enhance cancer treatment efficacy while reducing side effects. This approach aims to improve outcomes for patients resistant to current therapies.
Area of Science:
- Oncology
- Immunology
- Biomaterials Science
Background:
- Immune checkpoint inhibitors (ICIs) have transformed cancer therapy by harnessing the immune system.
- However, ICIs face challenges including ineffectiveness in some patients and significant immune-related adverse events (irAEs).
- Current administration methods lead to rapid systemic distribution, limiting therapeutic potential and increasing toxicity.
Purpose of the Study:
- To review advanced delivery strategies for ICIs to improve efficacy and reduce irAEs.
- To explore the potential of engineered biomaterials in enhancing local ICI delivery.
- To identify promising strategies for clinical translation of improved ICI delivery.
Main Methods:
- Review of preclinical and clinical studies on local ICI administration.
- Analysis of engineered biomaterial strategies for enhanced drug delivery (e.g., improved permeation, retention, targeting).
- Evaluation of tumor microenvironment-responsive systems and cell trafficking approaches.
Main Results:
- Local administration of ICIs shows potential for increased potency and reduced toxicity in preclinical models.
- Engineered biomaterials offer mechanisms to prolong drug retention and target tumor sites effectively.
- Strategies include antibody-mediated targeting, responsive systems, and cell-based delivery.
Conclusions:
- Engineered biomaterials hold significant promise for optimizing local ICI delivery.
- These advanced strategies can potentially overcome limitations of current ICI therapies, improving safety and efficacy.
- Further research and clinical translation are needed to realize the full potential of these innovative delivery systems.
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