通过 ENPP3 激活固有免疫.pdf

1、CD3 T Cell Engagers The Next Wave of IOCharles G.Drake,MD,PhD,MS,FAAP1Disclosure InformationCharles G.DrakeI am a paid employee of Johnson and Johnson Innovative MedicineI have an adjunct appointment at Columbia University,with ongoing clinical activities.I have an adjunct appointment at Johns Hopki

2、ns University,with ongoing mentorship roles.I will discuss investigational agents(but not off-label use)in my presentation.I am a co-inventor on a patent on LAG-3,licensed from Johns Hopkins University to Bristol Myers Squibb,with associated royalties.What is The Future of IO in Solid Tumors?Combine

3、d Immune Checkpoint Blockade(Nivo/Ipi,PD-1/LAG-3)Autologous CAR-T Allogeneic CAR-T Antibody Drug Conjugates CD3 T Cell Engagers(TCE)CD3 T Cell Engagers Proximity AND Activation 4Myeloma CellT cellGPRC5DTalquetamabCD3Cell DeathActivationPerforin and GranzymesThree Shots on GoalHarpoon HPN-24Janssen J

4、nJ-081Regeneron REGN5678Tumor Cell BindingHalf-lifeExtensionAnti-HSA sdAb Anti-PSMAAnti-CD3Anti-PSMAAnti-CD28Anti-PSMAT Cell EngagementAnti-CD3 scFvFierce Biotech:3/22“Harpoon drug sunk by modest activity,challenging tolerability,forcing pivot from prostate cancer prospect”Lim et al,Clinical Genitou

5、rinary Cancer,Vol.21,No.3,366375 2023Fierce Biotech:8/23“Regeneron rethinks CD28 bispecific R&D plan after 2 patients die”Xaluritamig:A Breakthrough for CD3 RedirectorsIn”Cold”TumorsCancer Discovery,2024Anti-STEAP1Anti-CD3Anti-STEAP1CRS Is Common with Xaluritamig8Normal TissuesTumor TissuesKLK2PSMAS

6、TEAP1ProstateProstate CancerHuman Kallikrein-2(hK2,KLK2)Serine protease(activates KLK3/PSA)Involved in semen liqueficationRegulated by AR(colocalizes with KLK3 on chromosome)Internal data confirmed its cell surface expressionhK2(KLK2):A Nearly Perfect Solid Tumor AntigenShen,F.Drake C.et al,Clinical