01.25.22

Durable Antitumor Immunity With PRDM1 Knockout

Yoshikawa T, Wu Z, Inoue Satoshi, et al. Genetic Ablation of PRDM1 in Antitumor T Cells Enhances Therapeutic Efficacy of Adoptive Immunotherapy. Blood. 2021; (doi: 10.1182/blood.2021012714).

Adoptive immunotherapy typically elicits a favorable but short-lived response in patients with advanced cancer, but researchers believe a more durable effect is possible through ablation of a key epigenetic gene. That gene, PR domain zinc finger protein 1 (PRDM1), is implicated in the progressive differentiation of antitumor T cells that ultimately causes loss of longevity. Genetic knockout of PRDM1 creates superior antitumor T-cells by enabling the acquisition of gene expression profiles of early memory T cells. It also accomplishes this by promoting the expansion of less differentiated chimeric antigen receptor (CAR)-engineered T cells in vivo, thus increasing T-cell persistence, which is necessary for a sustained therapeutic response. This approach promises to be viable for a range of adoptive cancer immunotherapies, researchers report.

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