Abstract: The invention relates to nucleic acid constructs comprising a combination of a first sequence encoding a CAR and second sequence encoding an amino acid transporter, and to cells comprising such nucleic acid constructs. It also relates to methods of manufacturing said cells, and to pharmaceutical compositions comprising said nucleic acid constructs or cells, for use in the treatment of diseases with cellular amino-acid depletion such as cancer.

Abstract: The invention relates to fusion target-binding proteins, such as chimeric antigen receptors (CARs), that comprise a target binding moiety, an intracellular signalling region, and an arginase domain. These proteins confer advantages that include improved cell killing and increased proliferation. The invention also relates to nucleic acids encoding the fusion target-binding proteins and cells expressing such proteins. The invention relates to pharmaceutical compositions, medical uses, and methods of treatment, all using the fusion target-binding proteins, cells, or nucleic acids disclosed. The medical uses and methods of treatment are of particular benefit in cancer therapy.

Abstract: Provided are fusion target-binding proteins comprising a target binding moiety, an intracellular signalling region and a domain that promotes synthesis of arginine or an arginine precursor. The domain may be an enzyme domain such as an argininosuccinate synthase (ASS-1) enzyme domain, or an ornithine transcarbamylase (OTC) enzyme domain. Also provided are cells comprising such a fusion target-binding protein (for example cells that express the fusion target-binding protein), and nucleic acids encoding such fusion target-binding proteins. The invention also provides fusion target-binding proteins comprising a target binding moiety, an intracellular signalling region and a domain that promotes synthesis of tryptophan or a tryptophan precursor. Pharmaceutical compositions, medical uses, and methods of treatment, all using the fusion target-binding proteins, cells, or nucleic acids are disclosed.

Abstract: A method of protecting a mammalian subject against, or treating, a disease, wherein the mammalian subject has elevated numbers and/or activities of MDSC comprising administering to the subject a pharmaceutically acceptable amount of an iNKT agonist, such as alpha galactosylceramide or an analogue thereof, or a TLR agonist, or a combination thereof.