A Biological Entity for Treating Brain Cancer

Smart overview of the Invention

A novel biological entity has been developed for the treatment of brain cancer, specifically targeting glioma. This construct features anti-tumor transgenes that include multiple GluA knockdown agents and is designed to enhance immune responses against glioblastoma cells. The entity is integrated into a modified vector based on the wild-type HSV-1 virus, where the ICP 34.5 gene is replaced with this new construct, allowing for selective infection of tumor cells while sparing healthy neurons.

Current Treatment Landscape

Glioma, particularly glioblastoma (GBM), is a highly aggressive form of brain cancer with limited treatment options. The standard treatment, temozolomide, offers only marginal improvements in survival rates. While there have been various trials exploring oncolytic viruses (OVs) for glioma treatment, none have yet reached the stage of randomized clinical trials. The unique challenges posed by the blood-brain barrier and the invasive nature of glioma necessitate innovative approaches like OVs that can be administered directly to the tumor site.

Mechanism of Action

The engineered HSV-1 virus utilizes a mechanism that targets neuron-tumor synapses to inhibit glioma cell proliferation. By delivering GluA1 and GluA2 knockdown agents, the biological entity disrupts the trafficking of AMPA receptors essential for tumor maintenance and growth. This targeted approach not only aims to slow tumor progression but also seeks to stimulate a robust anti-tumor immune response through the inclusion of immune checkpoint inhibitors in its design.

Preferred Embodiments and Efficacy

The preferred embodiment of this biological entity includes specific genetic interference targeting AMPA receptor subunits, which are crucial for communication between neurons and glioma cells. By preventing the proper functioning of these receptors at synapses, the OV aims to enhance its therapeutic efficacy. The intratumoral injection method is proposed to maximize local effects and improve overall survival rates compared to existing therapies.

Conclusion

This innovative biological entity represents a significant advancement in glioma treatment strategies by leveraging oncolytic virus technology combined with targeted gene therapy. Its design aims not only to attack tumor cells directly but also to enhance immune responses against them, offering hope for improved outcomes in patients battling this challenging form of cancer.