In a groundbreaking advancement for cancer immunotherapy, researchers have engineered lymph-node-inspired hydrogels that significantly enhance the activation, gene expression, and proliferation of CAR T cells. This innovation could revolutionize CAR T cell manufacturing, making the therapy more efficient and cost-effective.
Published in ACS Applied Materials & Interfaces, the study was conducted by scientists from the Institute of Materials Science of Barcelona (ICMAB-CSIC) and the Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)-Hospital Clínic de Barcelona.
Enhancing a Promising Cancer Immunotherapy
CAR T cells—chimeric antigen receptor T cells—are genetically modified immune cells designed to detect and destroy cancer cells. These living, patient-specific therapies have already shown significant success in treating leukemia and lymphoma and are now being investigated for broader oncological applications.
Traditionally, scientists manufacture CAR T cells using suspension cultures. However, this method presents challenges in efficiency and scalability. Addressing this issue, the ICMAB and IDIBAPS research teams have developed a new approach using bioengineered poly(ethylene glycol)-heparin hydrogels that mimic the structure and mechanical properties of lymph nodes.
Biomimetic Hydrogels Drive Better Results
As reported by medicalxpress, the novel hydrogels feature interconnected pores and tissue-like stiffness, creating a supportive environment for T cells to activate and proliferate—much like they do within human lymph nodes.
In laboratory testing, these hydrogels boosted the percentage of CAR+ cells by 50% and doubled the replication index compared to conventional suspension cultures. This indicates a remarkable improvement in both the quality and yield of therapeutic CAR T cells.
“By recreating key aspects of the lymph node microenvironment, our hydrogels provide the biochemical and mechanical cues necessary for enhanced CAR expression and T cell proliferation,” stated Dr. Judith Guasch, group leader of the Dynamic Biomaterials for Cancer Immunotherapy group at ICMAB and co-author of the study. “This approach could not only improve current CAR T cell products but also reduce manufacturing costs, making therapies more accessible.”
Optimizing Gene Transfer with Viral Vectors
To engineer CAR T cells, researchers must insert the CAR gene into T cells—commonly using lentiviral vectors. This step often presents variable outcomes, impacting the efficiency of CAR T cell production.
In this study, Dr. Jordi Faraudo from ICMAB’s Theory & Simulation group conducted theoretical simulations. These revealed that the hydrogel’s heparin component carries a negative charge. It interacts electrostatically with the positively charged VSV-G proteins on viral particles. This interaction facilitates greater contact between the virus and T cells, improving gene transfer efficiency.
“Our simulations show that heparin strongly attracts lentiviral particles and brings them into closer proximity with T cells, significantly enhancing CAR gene delivery,” Dr. Faraudo explained.
Bridging Disciplines to Advance Cell Therapies
This research exemplifies how integrating biomaterials engineering with theoretical modeling can create transformative solutions for cell-based therapies. The lymph-node-inspired hydrogels offer a scalable, effective alternative to current CAR T cell manufacturing methods. This innovation could potentially expand the therapy’s reach in oncology and beyond.
The study underscores the value of interdisciplinary collaboration. It also opens new pathways to improve the clinical viability of next-generation immunotherapies.