Innovative Biomimetic Hydrogels Enhance CAR T Cell Immunotherapy

Researchers have successfully developed advanced hydrogels inspired by lymph node structures that significantly improve the activation, gene expression, and proliferation of CAR T cells. This groundbreaking innovation holds the potential to streamline the production of CAR T cells, a promising cancer immunotherapy, by providing a more efficient and cost-effective manufacturing platform.

The study, published in ACS Applied Materials & Interfaces, was a collaborative effort between the Institute of Materials Science of Barcelona (ICMAB-CSIC) and the August Pi i Sunyer Biomedical Research Institute (IDIBAPS) at Hospital Clínic de Barcelona. CAR T cells, or chimeric antigen receptor T cells, are specialized immune cells that have been genetically modified to target and eliminate cancer cells. By equipping T cells with synthetic receptors that specifically recognize molecules on tumor cells, these personalized therapies have shown remarkable success in treating certain types of leukemia and lymphoma and are being investigated for broader applications.

The ICMAB research team has engineered innovative poly(ethylene glycol)-heparin hydrogels, characterized by interconnected pores and tissue-like stiffness. These hydrogels mimic the natural architecture of lymph nodes, where T cells typically activate and proliferate. Laboratory tests have shown that these hydrogels can increase CAR expression and T cell proliferation substantially compared to traditional suspension cultures, demonstrating a 50% increase in CAR-positive cells and doubling the replication index.

By replicating essential features of the lymph node microenvironment, these hydrogels create biochemical and mechanical cues that are crucial for enhancing CAR expression and T cell growth. This progressive approach not only promises to enhance the quality of current CAR T cell products but also aims to reduce manufacturing costs, thereby increasing accessibility to these therapies.

In the CAR T cell production process, introducing the CAR gene into T cells is typically achieved using lentiviral vectors, which are engineered viruses that deliver genetic material safely into cells. However, this gene transfer process is complex and often yields variable results in CAR T cell therapy. The study's theoretical simulations, led by experts at ICMAB, demonstrated that heparin--a negatively charged component of the hydrogel--binds electrostatically to the positively charged VSV-G proteins present on viral particles, enhancing their interaction with T cells and improving gene transfer efficiency.

These findings reveal a novel method to boost CAR T cell production by optimizing the environment for gene delivery, without altering the viral vectors themselves. This interdisciplinary collaboration highlights the integration of materials science and theoretical modeling as a pathway to advance cell-based therapies, emphasizing the potential of bioengineered hydrogels to make CAR T cell therapies more efficient, scalable, and accessible for clinical applications in oncology and beyond.