California: Xyphos Biosciences Inc. recently announced the issuance of U.S. Patent No. 10,259,858, entitled “Insertable Variable Fragments of Antibodies and Modified Alpha 1-Alpha 2 Domains of NKG2D Ligands and Non-Natural NKG2D Ligands that Bind Non-Natural Receptors.”

This patent, based on inventions by Xyphos scientists and issued to Xyphos, covers its ACCEL technology platform and includes broad composition-of-matter claims for its cell therapy products. Using this technology, company researchers are working toward programming a patient’s own immune cells to attack tumour cells with greater specificity and potentially lower toxicity compared to currently available cell therapies.

Commenting on the issue, James Knighton, Chief Executive Officer of Xyphos said, “This powerful technology should enable us to address several key issues that have arisen in first generation cell therapies, such as cancer relapse, side effects, cell exhaustion and the inability to target solid tumours.”

“We have an elegant, validated solution to targeting and controlling cells that does not require the engineering of complex intracellular machinery. Instead, our modular approach is easy to translate into treatments and capable of addressing multiple tumour targets, providing versatility and flexibility in order to successfully treat different cancers,” he added.

Unlike the first generation of approved cell therapies and complicated intracellular engineering approaches, the ACCEL technology is designed to allow greater flexibility in targeting tumour cells and control of the activity of cell therapy products. In addition, the platform provides for the specific functional modulation of those products. Xyphos’ solution is readily modifiable for use with different therapeutic cell types and varied tumour targets.

The ACCEL (Advanced Cellular Control through Engineered Ligands) platform enables precise control of activity and targeting of Xyphos’ universal CAR-T cell, termed convertibleCAR-T cell. Xyphos’ convertibleCAR technology exploits a powerful immune surveillance pathway involving NKG2D receptors that are naturally present on different cell types within the immune system including natural killer (NK) cells and some T-cells.

Through protein engineering, Xyphos engineered the natural receptor to be inactive until “turned-on” by a proprietary bispecific antibody also engineered by Xyphos, called a MicAbody protein. Once the MicAbody protein is introduced, one end binds exclusively to the inactive receptors on the convertibleCAR-T cell while the other binds the target on the malignant cell, activating the convertibleCAR-T cell to aggressively destroy it.

The resulting platform enables a single CAR-T cell to be precisely controlled and targeted to any specific antigen-expressing cell of choice using one or more tumour-specific MicAbody proteins. Using bispecific MIC-effector fusions (MicAdaptor™ proteins), Xyphos can externally deliver critical functionality (e.g. cytokine stimulation, checkpoint blockade, cell ablation, imaging agents, etc.) specifically to the Xyphos convertibleCAR-T cells.

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