UCLA researchers in the Department of Bioengineering have developed a novel microfluidic device that produces synthetic viscoelastic cells for efficacious therapeutic T cell activation.
BACKGROUND:
T cell-based therapies, such as the chimeric antigen receptor (CAR) T cell therapy, represents a significant advancement in cancer treatment, particularly for hematologic malignancies. The current market value for T cell-based therapies is estimated to be over $2 billion dollars and is expected to markedly increase in the upcoming years. A pivotal step in the development of these therapies involves the ex vivo priming of T cells to recognize and attack cancer cells. In vivo, T cells are activated through interactions with antigen-presenting cells (APCs). In vitro, this process is mimicked using artificial constructs like Dynabeads, which are polystyrene beads coated with antibodies targeting CD3 and CD28 molecules on the T cell surface, serving to stimulate the immune response. However, the efficacy of Dynabeads in T cell expansion and activation is somewhat compromised by their rigid, non-biological nature, which is less optimal compared to the pliability and viscoelasticity of natural APCs. Therefore, the development of more biologically representative and scalable technologies that mimic the physical properties of APCs holds significant promise for enhancing the effectiveness and reducing the costs of T cell activation in therapeutic applications.
INNOVATION:
Researchers at UCLA have developed the first scalable platform technology capable of producing viscoelastic microspheres for the use of T cell engineering. The state-of-the-art microfluidic device forms the Synthetic Viscoelastic Activating Cells or SynVACs. The device allows for precise control of viscoelasticity and mechanical properties to most resemble APCs. Experiments have found that SynVACs are superior to commercial Dynabeads in T cell activation, T memory stem cell formation, and chimeric antigen receptor (CAR) introduction into T cells. Importantly, due to these capabilities, SynVACs ultimately leads to long-lasting immunity against tumors, marking a significant advancement in the field of immunotherapy.
POTENTIAL APPLICATIONS:
- T cell activation for engineering T cell products, such as CAR-T cell products
ADVANTAGES:
- Well-defined viscoelasticity that more closely resembles endogenous APCs, providing a more natural stimulatory environment for T cells.
- Increased efficacy in T cell activation and stem cell formation, ensuring a robust immune response.
- Enhanced CAR transduction efficiency ensures that the same dosage of T cell infusion produces a significantly increased quantity of CAR-T cells, amplifying the effectiveness of targeted cancer treatments.
- The production of long-lasting immunity, offering prolonged protection against tumors and potentially reducing the need for repeated treatments.
DEVELOPMENT-TO-DATE:
Prototype microfluidic device have been built and assessed for efficacy of T cell activation, T memory stem cell formation, and chimeric antigen receptor (CAR) introduction into T cells.
Related Papers (from the inventors only)
Song Li, Zeyang Liu, Yan-Ruide Li et al. Synthetic Viscoelastic Activating Cells for T Cell Engineering and Cancer Therapy, 16 September 2023, PREPRINT (Version 1) available at Research Square [https://doi.org/10.21203/rs.3.rs-3338537/v1]