How to Design αβ T Cells Expressing γδ T Cell Receptors

As researchers delve deeper into the complexities of the immune system to harness its full potential, one remarkable development is the engineering of αβ T cells expressing γδ T cell receptors, offering a promising avenue for novel cancer therapies, and beyond.

Creative Biolabs explores the fascinating world of designing αβ T cells with γδ T cell receptors, shedding light on the techniques, challenges, and limitless possibilities this technology presents.

The Promise of αβ T Cells Expressing γδ T Cell Receptors

αβ T cells express T cell receptors (TCRs) composed of α and β chains. They are responsible for recognizing specific antigens presented by major histocompatibility complex (MHC) molecules, orchestrating a targeted immune response. γδ T cells express TCRs composed of γ and δ chains. They recognize a broader range of antigens, including stress-induced molecules and non-peptide antigens.

Fig. 1 αβ T cells engineered to express γδ T cell receptors.¹

Combining the unique features of αβ T cells and γδ T cells offers a tantalizing prospect for immunotherapy. By engineering αβ T cells to express γδ T cell receptors, we can

• Harness the antigen-recognition capabilities of γδ T cells
• Leverage the precision and memory of αβ T cells

Designing αβ T Cells Expressing γδ T Cell Receptors

• Selecting the Target Antigen
  The first crucial step is identifying the target antigen. This antigen should be specific to the disease or condition under consideration. Researchers must meticulously analyze the disease pathology to choose an antigen that is relevant and recognizable by γδ T cell receptors.
• Engineering γδ T Cell Receptors
  Once the target antigen is selected, the next step involves engineering the γδ T cell receptors. This can be achieved through various techniques, including genetic modification or chimeric receptor construction. The goal is to create receptors capable of binding to the chosen antigen with high affinity.
• Introducing γδ T Cell Receptors into αβ T Cells
  The engineered γδ T cell receptors are then introduced into αβ T cells. This can be achieved through viral transduction, electroporation, or other gene transfer methods. The key is to ensure successful integration of the γδ T cell receptors into the αβ-T cells.
• Characterization and Validation
  After the introduction of γδ T cell receptors, thorough characterization and validation of the modified αβ T cells is essential. This includes assessing their ligand reaction capabilities, cytotoxicity, and specificity.
• In Vivo and In Vitro Testing
  In vivo and in vitro functional assays are necessary after characterization and validation αβ T cells expressed desired γδ TCRs, mainly including but not limited to antigen affinity, cytotoxicity, and specificity.

Challenges and Future Directions

While the concept of designing αβ T cells expressing γδ T cell receptors holds immense promise, several challenges must be overcome.

• Optimizing receptor design
• Ensuring safety
• Addressing potential off-target effects

The field is advancing rapidly, with ongoing research paving the way for innovative solutions.

Creative Biolabs stands at the forefront of this revolutionary field, dedicated to pushing the boundaries of what is possible in the realm of T cell-based therapies. The potential for designing αβ T cells expressing γδ T cell receptors is limitless, offering new avenues to combat diseases and transform lives.

Together, contact us to harness the power of T cells in the immune system.

Reference

1. Strijker, Josephine GM, et al. "αβ-T cells engineered to express γδ-T cell receptors can kill neuroblastoma organoids independent of MHC-I expression." Journal of Personalized Medicine 11.9 (2021): 923.