abstract |
Target-binding fusion proteins are provided that comprise a target-binding moiety, an intracellular signaling region, and a domain that promotes the synthesis of arginine or an arginine precursor. The domain may be an enzymatic domain such as an argininosuccinate synthase (ASS-1) enzyme domain, or an ornithine transcarbamylase (OTC) enzyme domain. Also provided are cells comprising said target-binding fusion protein (eg, cells expressing the target-binding fusion protein), and nucleic acids encoding said target-binding fusion proteins. The invention also provides target-binding fusion proteins comprising a target-binding moiety, an intracellular signaling region, and a domain that promotes the synthesis of tryptophan or a tryptophan precursor. Pharmaceutical compositions, medical uses and method of treatment are disclosed, all using the target binding fusion proteins or nucleic acids. The proteins, cells, nucleic acids and pharmaceutical compositions can be used in the prevention and/or treatment of cancer, such as neuroblastoma or acute myeloid leukemia. |