Clinical Trial Purpose: This phase I study assessed the safety, pharmacokinetics (PKs), and efficacy of MIW815 (ADU-S100), a novel synthetic cyclic dinucleotide that activates the stimulator of IFN genes (STING) pathway, in patients with advanced/metastatic cancers....
PUBLICATIONS
Cost-Effectiveness of Immune Checkpoint Inhibitors in Urothelial Carcinoma-A Review
Review Over the last decade, an increasing number of immune checkpoint inhibitors (ICIs) have been assessed for therapeutic efficacy in urothelial carcinoma (UC). The high cost has prompted multiple cost-effectiveness analyses for the various disease stages, with no...
Lenvatinib plus pembrolizumab in patients with either treatment-naive or previously treated metastatic renal cell carcinoma (Study 111/KEYNOTE-146): a phase 1b/2 study
CLINICAL TRIAL Background: Despite advances in the first-line treatment of metastatic renal cell carcinoma (RCC), there is an unmet need for options to address disease progression during or after treatment with immune checkpoint inhibitors (ICIs). Pembrolizumab and...
A validated mathematical model of FGFR3-mediated tumor growth reveals pathways to harness the benefits of combination targeted therapy and immunotherapy in bladder cancer
Bladder cancer is a common malignancy with over 80,000 estimated new cases and nearly 18,000 deaths per year in the United States alone. Therapeutic options for metastatic bladder cancer had not evolved much for nearly four decades, until recently, when five immune...
Multi-step screening of neoantigens’ HLA- and TCR-interfaces improves prediction of survival
Improvement of risk stratification through prognostic biomarkers may enhance the personalization of cancer patient monitoring and treatment. We used Ancer, an immunoinformatic CD8, CD4, and regulatory T cell neoepitope screening system, to perform an advanced...
2-(4-Carbonylphenyl) benzoxazole inhibitors of CETP: attenuation of hERG binding and improved HDLc-raising efficacy
The development of 2-phenylbenzoxazoles as inhibitors of cholesteryl ester transfer protein (CETP) is described. Efforts focused on finding suitable replacements for the central piperidine with the aim of reducing hERG binding: a main liability of our benchmark...
Wnt-β-catenin activation epigenetically reprograms Treg cells in inflammatory bowel disease and dysplastic progression
The diversity of regulatory T (Treg) cells in health and in disease remains unclear. Individuals with colorectal cancer harbor a subpopulation of RORγt+ Treg cells with elevated expression of β-catenin and pro-inflammatory properties. Here we show progressive...
Germline genetic contribution to the immune landscape of cancer
Understanding the contribution of the host's genetic background to cancer immunity may lead to improved stratification for immunotherapy and to the identification of novel therapeutic targets. We investigated the effect of common and rare germline variants on 139...
Superoxide produced by mitochondrial site IQ inactivates cardiac succinate dehydrogenase and induces hepatic steatosis in Sod2 knockout mice
Superoxide produced by mitochondria has been implicated in numerous physiologies and pathologies. Eleven different mitochondrial sites that can produce superoxide and/or hydrogen peroxide (O2.-/H2O2) have been identified in vitro, but little is known about their...
Morphological correlation of urinary bladder cancer molecular subtypes in radical cystectomies
Several molecular subtypes of bladder cancer were identified with differing clinical behavior and responses to platinum-based chemotherapy. But so far, their urothelial histomorphologic features, besides association with some variant histologies, have remained fully...