EndureCART^TM: CAR-T Platform with Persistent Efficacy

CAR-T cell therapy is one of the most promising anti-cancer therapeutics, utilizing the body's immune system to combat cancer. However, challenges in solid tumor applications, such as the tumor microenvironment and cell heterogeneity, can diminish efficacy and potentially increase the toxicity of CAR-T therapy. To overcome these challenges, Protheragen has developed the EndureCART^TM technology platform. Through this innovative platform, we provide specialized services to clients in the CAR-T therapy sector, aiming to propel the advancement of the next generation of CAR-T therapies.

Overview of CAR-T Cell Therapy

CAR-T cell therapy is an immunotherapy technique that genetically modifies T-cells to express chimeric antigen receptors (CARs) that identify and attach to specific antigens on cancer cells. These CARs consist of extracellular domains for target recognition and intracellular domains to activate T-cells against cancer cells. Once reintroduced into the individual, these engineered CAR-T cells can effectively locate and eliminate cancer cells, offering a promising approach to cancer therapeutic.

Limitations of Conventional CAR-T Therapy:

Fig.1 Significant milestones in the development of CAR-T cell therapy. (Mitra, A., et al., 2023)

Introduction to the EndureCART^TM Platform

EndureCART^TM targets tumor metabolites or stromal proteins, recognizing the tumor microenvironment and activating T-cells sustainably by modifying the structure of chimeric antigen receptors, thus enhancing therapeutic efficacy. We have confirmed that CAR-T therapies targeting various targets, created using EndureCART^TM, exhibit enduring and effective anti-cancer properties.

The specific mechanism of action is that EndureCART^TM CAR-T cells with targeted effects penetrate tumor tissues, specifically recognize antigens, and trigger intracellular signaling pathways, prompting T-cell proliferation and cytokine release like IFN-1. This process reconstructs the tumor microenvironment, reversing immune suppression, and, with the collaboration of various immune cells, effectively eliminates tumor cells.

Fig.2 Mechanism of EndureCART^TM CAR-T therapy.

Durability of EndureCART^TM

The second-generation CAR comprises an activating domain and a co-stimulatory signaling domain like CD28 or 4-1BB. Leveraging the EndureCART^TM platform, we have developed an EDB-targeting CAR (EndureCAR-T) by fusing single-chain variable fragments to CD3ζ. This structure boosts downstream signaling mechanisms following CAR receptor activation, representing the fundamental advancement of EndureCART^TM.

This improved system can stimulate the STAT signaling pathway, with high-intensity JAK-STAT signaling activation dependent on tumor antigens, leading to continuous CAR cell proliferation and activation within tumor tissues. In contrast to the second-generation CAR-T cells, the EndureCAR enhances both T cell activation and the efficacy of tumor destruction in vitro and in vivo experiments.

Table. 1 Comparison of Conventional CAR-T with EndureCAR-T

Advantages of EndureCART^TM

• Long-lasting Effects

Ensuring sustained T-cell activation for enduring therapeutic outcomes.

• Memory Therapy

Boosting T-cell memory capabilities for persistent tumor cell elimination.

• High safety Standards

Maintaining high safety standards to reduce systemic toxicity and minimize therapeutic risks.

Our Services

By collaborating with us, you can utilize our technology platform to achieve long-term activation of CAR-T cells, accelerating project progress. In addition, we provide comprehensive CAR-T therapy development services, spanning from target identification and CAR molecular design to in vitro and in vivo efficacy evaluation and safety assessment.

Our mission is to optimize CAR-T cell activation using advanced technology and innovative platforms, driving the evolution of innovative CAR-T therapeutics to enhance safety and efficacy. If you are interested in our technology platform and services, please contact us for further information.

For research use only, not for clinical use.