Value Proposition:
· Significant cost savings and time savings compared to standard adoptive T cell therapies
· Improved accessibility for patients who cannot reach treatment centers offering adoptive T cell therapies
· Direct tumor targeting, limiting systemic clearance and minimizing off-target toxicity.
· Increased drug loading ratios of nearly 150% compared to standard nanoparticle-based delivery.
Unmet Need: Various immunological methods of eliminating cancer have been developed. One such method involves the activation of γδ T cells, which show promise due to their HLA-independent killing capability and long-lived, efficient cytotoxicity (Saura-Esteller, 2022). However, interest in utilizing γδ T cells has been limited by the challenges associated both with delivering and maintaining the activation of these cells (Zhang, 2023). With current technologies, cells must be isolated, expanded and activated ex vivo, and returned to the patient—a costly and resource-draining process that can only be performed in a limited number of clinics and hospitals. Furthermore, clinical trials with adoptively transferred γδ T cells have shown limited clinical success due to the loss of γδ T cell activation after adoptive transfer. To extend the durability of γδ T cell activation after transfer, patients have been treated with various regimens of bolus doses of γδ T cell-activating phosphoantigens. However, these attempts to boost γδ T cell activation after adoptive transfer were unsuccessful, due, in large part, to the poor tumor localization and retention of current phosphoantigen therapies (Hoeres, 2018). A superior strategy to adoptive therapy would be one that activated the patient’s endogenous γδ T cells population by maintaining γδ T cell-activating levels of phosphoantigen in the tumor microenvironment, resulting in γδ T cell trafficking to the tumor, durable γδ T cell-activation, and ultimately γδ T cell tumor killing. However, current delivery vehicles lack the physiochemical properties to efficiently encapsulate and/or deliver phosphoantigens, which are hydrophilic and have low molecular weights.
Technology Description: Researchers at Johns Hopkins have developed a polymeric nanoparticle prodrug delivery system for the activation of γδ T cells, stimulating their anti-cancer killing effect. By using improved molecular delivery and specifically targeting the tumor microenvironment, this method allows for a stronger and more reagent-efficient means by which to activate T-cells in situ and increase their localization to the tumor, resulting in enhanced and durable tumor killing. This method should also minimize toxicity caused by off-target immune activation, reducing adverse effects on patients. In addition to activating the patient’s endogenous γδ T-cell population, this technology can be used to maintain the activation of adoptively transferred ex vivo engineered γδ T-cells and other engineered cells bearing the γδ T receptor.
Stage of Development: Proof-of-concept completed. Animal pre-clinical testing underway in melanoma mouse models.
