一项针对肾细胞癌或尿路上皮癌患者的记忆样自然杀伤 (NK) 细胞免疫疗法的 0 期试点研究 (NCT06318871).pdf

1、Memory-like Natural Killer(NK)Cell Immune Therapy in Patients with Renal Cell Carcinoma or Urothelial Carcinoma(NCT06318871)Wenxin(Vincent)Xu,Wanling Xie,Fuguo Liu,Grace Birch,Casey Welch,Maily Nguyen,Mila Stanojevic,Srinivas R.Viswanathan,Bradley A.McGregor,Jerome Ritz,David A.Braun,Sarah Nikiforow

2、,Rizwan Romee*,Toni K.Choueiri*Introduction Single-cell analysis of RCC shows that dysfunctional NK cells,with impaired cytotoxicity and expressing tissue residency markers,are enriched in patients with advanced disease In two independent cohorts(TCGA and CheckMate 025),a gene expression signature d

3、erived from this dysfunctional NK cell population is associated with worse survival The Romee lab has shown that cytokine induced memory-like(CIML)NK cells have prolonged survival,proliferation,and cytotoxicity.Can we restore NK cell antitumor activity against RCC?Xu*,Birch*,Meliki*Romee*,Choueiri*,

4、Braun*.Progressive natural killer cell dysfunction in advanced-stage clear-cell renal cell carcinoma and association with clinical outcomes.ESMO Open.2025 Feb;10(2):104105.Trial DesignPrimary outcome:60%feasibility to collect cells,generate and administer CIML NK cells to patients5/10 patients have

5、been enrolled to dateKey eligibility:Advanced RCC(ccRCC,chRCC,tRCC)or UC Progression after prior PD-1 or PD-L1 inhibitorsVision/Impact This is the first trial to investigate cytokine induced memory-like natural killer cell therapy in RCC and UC Correlative studies funded by DOD CDMRP KCRP and KCA AD

6、A will explore the phenotype and function of NK cells and determinants of treatment response These data help to inform ongoing work on NK cell-based therapies IL-12/A3 fusion cytokine secreting CD70-CAR NK may further improve persistence an