On June 27, 2023 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported a publication in Cancer Immunology Research1 entitled: ‘Enhancing CAR T cell therapy using Fab-Based Constitutively Heterodimeric Cytokine Receptors (Press release, Autolus, JUN 27, 2023, View Source [SID1234632937]).’

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For CAR T cells to be effective, they must engraft in the patient, expand to sufficient numbers and persist at the site of disease. Often this can involve intervals in the absence of cognate antigen, for instance during trafficking, or in the face of a hostile tumor microenvironment. T cells in a physiological immune response are supported by a network of immune cells which provide cytokine signals to stimulate proliferation and survival. CAR T cells must survive in the absence of such networks.

To address this, Righi et al describe dFabCCR, a constitutive cytokine receptor architecture. dFabCCR is a highly versatile T cell engineering component which can transmit arbitrary cytokine signals to a CAR T cell: cytokine signals normally associated with T cells such as IL2 and IL7 can be transmitted, these maintain T cells as IL2/7 exposure would do. When screening a library of different cytokine dFabCCRs, other cytokine signals such as that from IL18 or even GM-CSF had distinct functional effects on CAR T cell biology which may have therapeutic advantages in some settings.

"Achieving sufficient CAR T cell expansion and persistence can be difficult when targeting solid cancer antigens," said Dr Martin Pule, Chief Scientific Officer and Founder of Autolus. "Development of the dFabCCR architecture allows us to supply CAR T cells with versatile constitutive cytokine signals overcoming a barrier to effective CAR T cell therapies for solid cancer and is another powerful entry in our toolkit of T cell engineering components."