Platform combines graphene oxide with antibodies to enhance CAR-T cell therapy

Oct 8, 2024 at 3:08 PM

Harnessing the Immune System's Superpowers: A Breakthrough in CAR-T Cell Therapy

Imagine a future where your own immune cells become powerful cancer-fighting allies, thanks to a revolutionary treatment called CAR-T cell therapy. This groundbreaking approach is already saving lives, but the journey to unlock its full potential comes with unique challenges. Now, a team of researchers has unveiled a game-changing tool that could make this therapy more effective and accessible, paving the way for a new era in the fight against cancer.

Unlocking the Immune System's Potential to Defeat Cancer

Bridging the Gap Between Lab and Reality

Current methods for activating T cells, a crucial component of the immune system, don't closely mimic the natural environment in which they interact with other immune cells. This connection is vital for activating T cells and amplifying their cancer-fighting abilities. Researchers at UCLA have developed a powerful platform that combines a flexible material called graphene oxide with specific antibodies, closely mimicking these natural interactions.

This innovative approach has shown a remarkable capacity for stimulating T cell proliferation while preserving their versatility and potency. "Our interface bridges the gap between the laboratory and actual conditions inside the body, allowing us to gain insights much more relevant to real-world biological processes," said co-corresponding author Yu Huang, the Traugott and Dorothea Frederking Professor of Engineering at the UCLA Samueli School of Engineering and a member of the California NanoSystems Institute at UCLA (CNSI).

Beyond T cell therapies, this technology has the potential to revolutionize a variety of fields, including tissue engineering and regenerative medicine. "We've developed an exciting new approach to boosting the effectiveness of T cell therapies," said co-corresponding author Lili Yang, a professor of microbiology, immunology and molecular genetics at the UCLA College, as well as a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA (BSCRC) and of the UCLA Health Jonsson Comprehensive Cancer Center.

Enhancing the Potency and Efficiency of CAR-T Cells

The researchers anchored two specific antibodies onto graphene oxide, creating a platform that facilitated a 100-fold-plus increase in T cell expansion in a culture of blood cells over 12 days. This technology also enhanced the efficiency of engineering immune cells, leading to a five-fold increase in CAR-T cell production compared to the standard process.

The team also identified several crucial biochemical pathways for T cell signaling and function that were activated by their technology, enabling the increase in growth and efficiency. "Our method enhanced the potency and efficiency of these cells in ways that weren't possible with traditional methods. This is particularly important for CAR-T cell therapy, where the strength and proliferation of T cells makes a significant difference in patient outcomes," said Yang.

Overcoming Dependence on External Factors

Traditionally, the lab-based portion of generating CAR-T cells requires the addition of a specific immune factor called autocrine interleukin-2, or IL-2. The researchers found that their platform stimulated the production of IL-2, potentially making that external addition unnecessary.

"We got very excited when we discovered that our method can overcome the dependence on external IL-2 supplementation," said UCLA postdoctoral fellow Enbo Zhu, co-first author of the study. "We confirmed that our rational design for mimicking an important immunological interaction is on the right track. It encourages us to dive deeper into developing its applications in CAR-T cell therapy."

Co-first author Jiaji (Victor) Yu, who earned a doctorate from UCLA in 2021, added, "This work depended on cross-disciplinary collaboration, merging the fields of immunology, materials science and engineering, nanotechnology and bioengineering. With teamwork like this, as well as innovation, perseverance, and a deep commitment to finding better ways to fight cancer, we're building a future where genetically engineered superpowers aren't just in comic books—they're in our hospitals, saving lives."