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Evolocumab as an immunomodulator in glioma: A window of opportunity trial evaluating PCSK9 inhibition to enhance surface MHC-I on tumor

ABSTRACT: Many cancers, including glioma, evade immunosurveillance by downregulating major histocompatibility class (MHC)-I expression. Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes intracellular degradation of multiple receptors, including MHC-I. Inhibition of PCSK9 (PCSK9i) blocks MHC-I degradation and potentiates immune checkpoint blockade (ICB) against multiple cancers in vivo. Evolocumab is an FDA approved PCSK9i monoclonal antibody (mAb) indicated for hyperlipidemia. However, mAbs have limited penetrance across the blood brain/tumor barrier (BBB/BTB). We therefore conducted a non-randomized surgical window-of-opportunity study to evaluate if pre-operative subcutaneous (SC) Evolocumab penetrates the blood-brain/tumor barrier to reach tumor and exert a biological effect (PesKE; NCT04937413). Four patients received pre-procedure evolocumab and had sufficient tissue for research, while 17 were analyzed as contemporaneous controls. Evolocumab was quantified in whole blood and tumor across by mass spectroscopy (LC-MS/MS).

ORGANISM(S): Homo Sapiens

SUBMITTER: Matt Foster

PROVIDER: PXD053215 | panorama | Sun Sep 21 00:00:00 BST 2025

REPOSITORIES: PanoramaPublic

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