Anti-CD30 Chimeric Antigen Receptor for Cancer-Selective Killing

The patent applies local quality by making the CAR T-cell response conditional on the local microenvironment. The T-cell only becomes activated and toxic when specific local conditions are met: presence of CD30 antigen AND specific co-stimulatory signals (4-1BB or OX40) from the target cell. This spatial and contextual specificity allows the same CAR T-cell to be non-toxic to healthy CD30+ cells that lack the proper microenvironmental signals, while being highly toxic to tumour cells that provide both CD30 and the necessary co-stimulatory context.

The patent introduces co-stimulatory domains (4-1BB or OX40) as intermediary signaling requirements. These domains act as mediators that must be engaged by specific ligands on the target cell to fully activate the CAR T-cell. This intermediary step creates an additional layer of specificity: healthy CD30+ cells that do not express the appropriate co-stimulatory ligands cannot activate the CAR T-cell, even though they express CD30. The intermediary co-stimulatory signal thus filters out off-target effects while preserving on-target efficacy against tumour cells.

The patent applies dynamics by making the CAR T-cell activation and cytolytic activity dynamically regulated rather than constitutively active. The T-cell remains in a low-activation state until it encounters the specific combination of CD30 and co-stimulatory signals, at which point it becomes highly active for tumour killing. After engagement, the T-cell can proliferate and persist long-term, transitioning between activation states as needed. This dynamic regulation allows the T-cell to maintain both high productivity when needed and long persistence when dormant.

The patent changes the activation parameters of the CAR T-cell by requiring dual signaling (CD30 binding plus co-stimulatory engagement) rather than single-signal activation. This parameter change creates a higher activation threshold that prevents spurious activation while allowing robust activation against true targets. The modified activation parameters enable the T-cell to sustain prolonged persistence and amplification capacity, as the higher threshold prevents exhaustion from constant low-level activation while maintaining the ability to mount strong productive responses against tumour cells.

The patent merges multiple functional domains into a single CAR construct. Instead of using separate first-generation CAR designs, the patent combines the CD30-specific antigen recognition domain with co-stimulatory domains (4-1BB or OX40) into an integrated chimeric receptor. This merging creates a unified structure that performs both antigen binding and co-stimulation functions, thereby improving T-cell persistence and amplification while maintaining relative structural simplicity. The merged design eliminates the need for separate co-stimulatory molecules and simplifies the signaling architecture.

The patent applies universality by designing the CAR to perform multiple functions through the co-stimulatory domains. The 4-1BB or OX40 domains provide not only co-stimulation for initial activation but also promote long-term T-cell survival, proliferation, and memory formation. This multi-functionality allows the same CAR structure to enhance both immediate tumour killing and long-term persistence, making the design universally applicable to improving CAR T-cell therapy outcomes without requiring entirely separate mechanisms for each function.