Antibody-Based Cell Expansion Technology For Large-Scale And Safe Amplification Of Gamma Delta T Cells

SUMMARY

Novel antibodies to rapidly and safely expand γδ T cells enabling large-scale production for cancer immunotherapies like γδ CAR-T cells, and potentially boosting these cells directly in patients

The Unmet Need: Efficient large-scale expansion of γδ T cells with enhanced safety profile

• Gamma delta (γδ) T cells represent a unique and promising subset of immune cells within the broader field of immunotherapy, particularly for cancer treatment. Unlike conventional alpha-beta (αβ) T cells, γδ T cells possess innate-like properties and can recognize and kill tumor cells without the need for antigen presentation via major histocompatibility complex (MHC) molecules. This makes them attractive candidates for adoptive cell therapies, including chimeric antigen receptor (CAR)-T cell approaches. However, the naturally low abundance of γδ T cells in peripheral blood has been a significant barrier to their widespread therapeutic use. Efficient and scalable methods for expanding γδ T cells are therefore highly sought after to unlock their full clinical potential.

• Current approaches for γδ T cell expansion, such as the use of small molecules like zoledronic acid, have demonstrated the ability to increase γδ T cell numbers but are associated with notable limitations. These small molecule-based methods can cause undesirable side effects, including toxicity and off-target immune activation, which restrict their clinical utility and safety. Moreover, the expansion efficiency and reproducibility of these methods can vary, making it challenging to achieve the large cell numbers required for commercial-scale manufacturing of γδ T cell therapies. As a result, there is a pressing need for safer, more reliable, and scalable techniques to expand γδ T cells for both research and therapeutic applications.

The Proposed Solution: Pan-specific antibodies targeting Vγ9Vδ2 T-cell receptor to robustly expand γδ T cells enabling commercial-scale production for γδ CAR-T cell therapies

• The faculty inventor developed pan-specific antibodies that target the Vγ9Vδ2 T-cell receptor (TCR) to achieve robust expansion of γδ T cells from peripheral blood mononuclear cells (PBMCs). When these antibodies are co-incubated with PBMCs, they induce a 40-50 fold increase in γδ T cell numbers within just 14 days, overcoming the natural scarcity of these therapeutically valuable cells. The approach is designed for commercial-scale cell expansion, making it particularly suitable for advanced immunotherapies such as γδ CAR-T cell treatments. In addition to ex vivo cell manufacturing, the technology also holds promise for direct in vivo administration, where the antibodies could be used to boost γδ T cell populations in patients, leveraging their innate anti-cancer properties.

• While small molecules can achieve similar expansion rates, they often come with undesirable side effects. The antibody approach circumvents these issues, providing a cleaner safety profile and greater specificity for γδ T cells. Furthermore, by enabling commercial-scale expansion, this solution addresses a major bottleneck in the development of γδ T cell-based therapies, paving the way for broader clinical adoption and new immunotherapeutic strategies.

ADVANTAGES

ADVANTAGES

• Enables 40-50 fold expansion of rare γδ T cells within 14 days, overcoming natural low abundance limitations

• Supports commercial-scale production of γδ T cells for therapeutic applications, including γδ CAR-T cell therapies

• Provides a safer alternative to small molecule-based expansion methods by avoiding associated side effects

• Utilizes pan-specific antibodies targeting the Vγ9Vδ2 T-cell receptor for selective and efficient cell proliferation

• Offers potential for direct in vivo administration to boost γδ T cell populations and enhance innate anti-cancer immunity

• Offers potential for direct in vivo administration to boost γδ T cell populations and enhance innate anti-cancer immunity

• Facilitates development of novel immunotherapies with improved safety and efficacy profiles

APPLICATIONS

• γδ CAR-T cell therapy manufacturing

• In vivo cancer immunotherapy

• Cell therapy for infectious diseases

• Research-grade γδ T cell supply