Evolution of CAR T-cell technology can be summarised as first-generation CARs consisting of the CD3ζ alone, the second generation including additional costimulatory signalling domains (CD28 or 4-1BB), the third generation combining two costimulatory domains, (e.g., CD28 and 4-1BB) [42], and the fourth generation additionally encoding a proinflammatory cytokine such as IL-12 or GM-CSF to enhance the immunogenicity of the tumour microenvironment and potentially recruit other innate immune cells [43]. The gene discussed is CD28; the disease is neoplasm.