Furthermore, these approaches need to be validated in pre-clinical studies including both long- and short- toxicity tests considering the characteristic, source and strategy of production of the effector cells used for the generation of CAR+ cells (polyclonal T cells, antigen-specific T cells, CD8+, a particular ratio of CD4+/CD8+, γ/δ T cells, NK-T cells or NK cells), for which, however, only limited data are now available on their metabolic response to the in vitro stimulation and their anti-tumor response. Here, CD4 is linked to neoplasm.