Publications by authors named "M M Dougan"
Long-standing goals of cancer immunotherapy are to activate cytotoxic antitumor T cells across a broad range of affinities while dampening suppressive regulatory T (Treg) cell responses, but current approaches achieve these goals with limited success. Here, we report a IL-21 mimic, 21h10, designed to have augmented stability and high signaling potency in both humans and mice. In multiple animal models and in human melanoma patient derived organotypic tumor spheroids (PDOTS), 21h10 showed robust antitumor activity.
View Article and Find Full Text PDFMacrophages engulf apoptotic bodies and cellular debris as part of homeostasis, but they can also phagocytose live cells such as aged red blood cells. Pharmacologic reprogramming with the SMAC mimetic LCL161 in combination with T cell-derived cytokines can induce macrophages to phagocytose live cancer cells in mouse models. Here we extend these findings to encompass a wide range of monovalent and bivalent SMAC mimetic compounds, demonstrating that live cell phagocytosis is a class effect of these agents.
View Article and Find Full Text PDFArticle Synopsis
- Tumor-infiltrating-lymphocyte (TIL) therapy can leverage the body's own T cells to fight tumors but has lengthy production processes that may reduce effectiveness.
- Researchers introduced a method using retroviral vectors paired with peptide-major histocompatibility complexes (pMHC) to deliver genes specifically to CD8 T cells, aiming to enhance their anti-tumor functions.
- The study showed that these pMHC-targeted viral vectors succeeded in activating and expanding effective anti-tumor T cells in mice, potentially simplifying the production of engineered cell therapies and improving survival rates in tumor-bearing models.
Background And Aims: Typical immune checkpoint inhibitor-induced colitis (T-ICI) has significant histomorphologic overlap with inflammatory bowel disease (IBD), a distinction further complicated in ICI-treated patients with pre-existing inflammatory bowel disease (P-IBD) and those with potentially "unmasked" inflammatory bowel disease (U-IBD) after ICI therapy. This study describes histopathologic findings seen in U-IBD colonic biopsies and assesses for distinguishing features from T-ICI and P-IBD biopsies.
Methods: Initial colon biopsies after symptom onset from 34 patients on ICI therapy were reviewed, and histopathologic features were tabulated.
Article Synopsis
- Current methods for identifying immune-related adverse events (irAEs) in patients undergoing immune checkpoint inhibitor (ICI) therapy are not very effective, but large language models (LLMs) show promise in improving this process.
- In a study, LLMs were compared to manual reviews and ICD codes for detecting common irAEs in hospitalized patients, demonstrating significantly higher sensitivity especially for conditions like hepatitis and myocarditis.
- The LLM was faster in analysis—averaging 9.53 seconds per chart compared to 15 minutes for manual adjudication—indicating that LLMs could be a valuable tool in clinical settings for accurately identifying irAEs.