Chimeric Switch Receptors for the Conversion of Immunosuppressive Signals to Costimulatory Signals Turning a Tumour's "Off" Switch Into a "Go" Signal for Engineered Immune Cells

This patent describes chimeric switch receptors, a class of engineered proteins designed to flip an inhibitory signal that normally shuts down an immune cell into a signal that activates it instead. The receptors are intended for use in engineered immune cells such as CAR T cells, giving cancer cell therapies a way to keep working inside the hostile environment of a tumour.

The Problem

One of the biggest obstacles in cancer immunotherapy is that tumours actively switch off the immune cells sent to destroy them. They do this by displaying molecules such as PD-L1 and by releasing TGF-beta, which bind to inhibitory receptors on T cells and tell them to stand down. The region around a solid tumour, known as the tumour microenvironment, is rich in these suppressive cues. As a result, even powerful engineered cell therapies can become exhausted and ineffective once they arrive at the tumour.

What This Invention Does

The patent provides chimeric switch receptors that are built from two parts joined together. The outward-facing part comes from an inhibitory receptor such as PD-1 or a TGF-beta receptor, so it still senses the tumour’s suppressive signals. The inward-facing part comes from one or more costimulatory proteins such as CD2, CD28, ICOS, MyD88 or DAP10, which normally tell an immune cell to ramp up. By fusing them, the receptor catches a “stop” signal at the surface and converts it into a “go” signal inside the cell.

The patent also covers immune cells engineered to carry these receptors, often alongside a chimeric antigen receptor and an optional chimeric cytokine receptor, plus the methods of making the cells and using them to treat disease.

Key Features

• Signal conversion design. The receptor turns an immunosuppressive input such as PD-L1 or TGF-beta into a costimulatory output that energises the cell.
• Modular building blocks. The inhibitory sensing domain and the costimulatory signalling domain can be mixed and matched from a defined menu of well-characterised proteins.
• Combination with CAR therapy. The switch receptors are designed to work in the same cell as a chimeric antigen receptor, supporting more durable tumour killing.
• Optional cytokine support. The engineered cells can also carry a chimeric cytokine receptor to further sustain their activity.
• Full therapeutic package. The claims extend to the engineered cells, the populations of cells, and the methods of manufacturing and treatment.

Who Is Behind It

The applicant is Allogene Therapeutics, Inc., a clinical-stage biotechnology company based in South San Francisco that develops “off the shelf” allogeneic CAR T cell therapies intended to be ready for patients without custom manufacturing per person. The named inventors are Yi Zhang, Silvia K. Tacheva-Grigorova, Barbra Johnson Sasu, Siler Panowski, Regina Junhui Lin and Zhe Li. The application is a divisional of an earlier filing.

Why It Matters

Solid tumours have been a stubborn barrier for cell therapies that work well in blood cancers. A receptor that does not just resist suppression but actively feeds on it could help engineered immune cells stay active exactly where they tend to fail. Securing the intellectual property in Australia protects Allogene’s position for any clinical development, manufacturing or licensing it pursues in the region.

Related Concepts

• Chimeric antigen receptor T cell – the engineered cell platform these receptors are designed to strengthen.
• Immune checkpoint – the braking system tumours exploit to switch off T cells.
• Tumour microenvironment – the suppressive setting around a solid tumour.
• T cell costimulation – the activating second signal the receptor recreates.
• Cancer immunotherapy – the broader field this invention sits within.

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AU 2026201894 was published in the Australian Official Journal of Patents on 2 April 2026 and is open for public inspection. Patent applications represent inventions that are sought to be protected and do not necessarily reflect commercially available products.