PRMT7-specific PROTAC degrader achieves improved adoptive cancer immunotherapy by enhancing CD8+ T effector function through NF-kB activation.

Herein we report that deletion of Prmt7 in T cells in mice with CD4-Cre increased CD8+ T effector cell cytokine production, cytolytic activity and anti-tumor activity of CTLs by transcriptional reprogramming. We show that Prmt7-deficiency in CTLs reprograms the CD8+ T cells with many transcription factors allowing them to exhibit increased proliferation, and express effector molecules.

To translate these findings into a potential clinically applicable treatment, we generated a PRMT7 PROTAC degrader (MS54). We show that CTLs treated with the MS54 had similar reprogramming as the Prmt7 cKO CTLs. Adoptive cell transfer of MS54-treated CTLs from OT-I mice significantly enhanced their anti-tumor activity in a syngeneic melanoma murine cancer model.