Publications by authors named "S Topalian"
Article Synopsis
- Gastric carcinomas (GCs) are aggressive cancers, with only 15% of patients responding to anti-PD-(L)1 treatments, but those associated with Epstein-Barr virus (EBV) exhibit better responses and unique immune characteristics.
- A study analyzed tumor immune microenvironments in 25 treatment-naïve GCs, comparing 11 EBV+ and 14 EBV- cases using immunohistochemistry and gene expression profiling.
- Results showed EBV+ GCs had higher densities of CD8+ T cells and distinct immune gene expression patterns, while EBV- GCs demonstrated increased inflammatory and immunosuppressive gene signatures, suggesting differing mechanisms of immune evasion.
Article Synopsis
- Nivolumab (NIVO) combined with ipilimumab (IPI) shows better long-term overall survival (OS) in patients with unresectable/metastatic melanoma than NIVO alone, based on pooled data from major trials.
- Patients treated with the combination therapy had a median follow-up OS of 45.0 months, with 6-year survival rates at 52%, compared to 41% for NIVO monotherapy after a median follow-up of 35.8 months.
- Clinical factors affecting survival include elevated lactate dehydrogenase (LDH) levels, age over 65 with the combination therapy, and presence of liver metastases with NIVO alone.
Merkel cell carcinoma (MCC) is a highly immunogenic skin cancer primarily induced by Merkel cell polyomavirus, which is driven by the expression of the oncogenic T antigens (T-Ags). Blockade of the programmed cell death protein-1 (PD-1) pathway has shown remarkable response rates, but evidence for therapy-associated T-Ag-specific immune response and therapeutic strategies for the nonresponding fraction are both limited. We tracked T-Ag-reactive CD8+ T cells in peripheral blood of 26 MCC patients under anti-PD1 therapy, using DNA-barcoded pMHC multimers, displaying all peptides from the predicted HLA ligandome of the oncoproteins, covering 33 class I haplotypes.
View Article and Find Full Text PDFBackground: In preliminary findings from the recurrent or metastatic cervical cancer cohort of CheckMate 358, nivolumab showed durable anti-tumour responses, and the combination of nivolumab plus ipilimumab showed promising clinical activity. Here, we report long-term outcomes from this cohort.
Methods: CheckMate 358 was a phase 1-2, open-label, multicohort trial.
Raman spectroscopy and one-dimensional convolutional neural network modeling as a real-time monitoring tool for in vitro transaminase-catalyzed synthesis of a pharmaceutically relevant amine precursor.
Biotechnol Prog
June 2024
Raman spectroscopy has been used to measure the concentration of a pharmaceutically relevant model amine intermediate for positive allosteric modulators of nicotinic acetylcholine receptor in a ω-transaminase-catalyzed conversion. A model based on a one-dimensional convolutional neural network was developed to translate raw data augmented Raman spectra directly into substrate concentrations, with which the conversion from ketone to amine by ω-transaminase could be determined over time. The model showed very good predictive capabilities, with R values higher than 0.
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