Provided is a modified T lymphocyte (CAR-T lymphocyte) which allows for tumour cell specific cytotoxicity, comprising: a. a first polypeptide comprising a first extracellular antigen binding domain that binds a first antigen, and a first intracellular signaling domain that comprises an immunoreceptor tyrosine-based activation motif (ITAM), and wherein said first polypeptide does not comprise a co-stimulatory domain； and b. a second polypeptide comprising a second extracellular antigen binding domain binding a second antigen, or a receptor that binds said second antigen； and a second intracellular signaling domain that comprises one or more co-stimulatory domains but not an ITAM； or a. a first polypeptide comprising a first extracellular antigen binding domain that binds a first antigen, and a first intracellular signaling domain that comprises one or more co-stimulatory domains but not an immunoreceptor tyrosine-based activation motif (ITAM)； and b. a second polypeptide comprising a second extracellular antigen binding domain binding a second antigen, or a receptor that binds said second antigen； and a second intracellular signaling domain, that comprises an ITAM, wherein said second polypeptide does not comprise a co-stimulatory domain； wherein: said first antigen is an antigen on a tumor cell, a tumor-associated antigen, or a tumor-specific antigen； the second antigen is vascular endothelial growth factor (VEGF) or a damage associated molecular pattern molecule (DAMP)； and said modified lymphocyte becomes maximally cytotoxic only when said first signaling domain and said second signaling domain are both activated by said first antigen and said second antigen, respectively.
