We demonstrate that CRISPR/Cas9-mediated knockout of PRDM1 not only successfully depletes HAVCR2-expressing CD8+ T-cell and increases TCF7-expressing CD8+ gene signatures during manufacturing, but also substantially enhances in vivo CAR T-cell proliferation and increased frequencies of TIM-3−TCF1+CD8+ peripheral blood and tumor-infiltrating CAR T-cells. Here, TCF7 is linked to neoplasm.