Chimeric antigen receptor (CAR)-T cell therapy has drastically changed the treatment landscape for B cell malignancies. Whilst (CAR)-T cell therapy holds great promise for the treatment of solid cancers, additional challenges associated with the tumour microenvironment, tumour antigen expression and T cell trafficking and persistence have prevented similar advances so far. Promoting a stem-like phenotype has been documented to improve CAR-T persistence, proliferation and cytokine production. We have observed that the presence of TSCM CD4+ CAR-T cells is critical to preserve TSCM CD8+ CAR-T function, however the mechanism behind this beneficial interaction is currently unknown. We performed transwell assays to determine whether this effect is contact-dependent or involved soluble mediators. Cell-cell contact between CD4+ and CD8+ LeY+ CAR-T cells promoted CD8+ CAR-T proliferation. Bulk RNA sequencing comparing CD8+ CAR-T cells produced in contact with CD4+ CAR-T cells, or cells separated by a transwell membrane, revealed increased expression of T cell activation and proliferation genes, including CCR7, BATF3, IL12RB, LIF, CALM3, ADA, LIG3 and ATF6B. A knock-out CRISPR library screen of T-cell associated genes has also been performed to analyse the effect of CD4+ on CD8+ naïve T cells, and the top hits from this screen will be presented.