Multimodal stratification of predictive biomarkers in head and neck cancers: A focus on cytokine-based immunotherapy

 

Explore our recent poster presentation, which discusses the challenge of identifying predictive biomarkers for cytokine-based immunotherapy in head and neck cancers due to the complexity of biological systems and cancer pathophysiology. It highlights the importance of understanding how drugs interact with different biomarkers and tissues spatially to improve trial success rates, reduce costs, and accelerate completion times.

By analyzing spatial and temporal changes in tumor cells and their microenvironment, you can uncover resistance mechanisms, leading to the design of more effective combination therapies. The Aliri solution offers enhanced tumor profiling through spatial analysis, integration of heterogenous data types, and predictive analysis, ultimately identify robust biomarker signatures for improved immunotherapy outcomes.

Download our poster to gain insights into the unique biomarker signatures correlated with therapy response.

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Keeping an eye on molecular imaging: drug efficacy & toxicity in ophthalmology

 

Discover how Mass Spectrometry Imaging (MSI) is revolutionizing preclinical studies by offering quick and accurate assessments of ocular treatments’ efficacy and safety.

With MSI, track the bio-distribution of drugs and metabolites while pinpointing biomarkers for efficacy or toxicity. Gain valuable insights into ocular drug distribution and biomarker modulation with Aliri’s advanced MSI technology.

Download our application note to dive deeper into our MSI technology and its applications in ocular diseases.

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Coproporphyrin-I and Coproporphyrin-III

 

Aliri Bioanalysis presents a newly validated non-proprietary biomarker assay (NPA) for the quantitation of Coproporphyrin I and Coproporphyrin III in human plasma. This assay offers significant advancements in biomarker analysis, applicable across diagnostics, pharmaceutical research, and patient care.

By monitoring these biomarkers, particularly in early clinical development, companies can assess OATP1B1 inhibition, potentially avoiding the need for dedicated clinical drug-drug interaction studies, saving both time and money.

Learn more about the benefits of our NPA for Coproporphyrin I and Coproporphyrin III.

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Mercapturate pathway metabolites of sotorasib, a covalent inhibitor of KRAS G12C , are associated with renal toxicity in the Sprague Dawley rat

 

Sotorasib is a first-in class KRAS G12C covalent inhibitor in clinical development for the treatment of tumors with
the KRAS p.G12C mutation. In the nonclinical toxicology studies of sotorasib, the kidney was identified as a
target organ of toxicity in the rat but not the dog. Renal toxicity was characterized by degeneration and necrosis
of the proximal tubular epithelium localized to the outer stripe of the outer medulla (OSOM), which suggested
that renal metabolism was involved. Here, we describe an in vivo mechanistic rat study designed to investigate
the time course of the renal toxicity and sotorasib metabolites. Renal toxicity was dose- and time-dependent,
restricted to the OSOM, and the morphologic features progressed from vacuolation and necrosis to regeneration
of tubular epithelium. The renal toxicity correlated with increases in renal biomarkers of tubular injury.
Using mass spectrometry and matrix-assisted laser desorption/ionization, a strong temporal and spatial associ –
ation between renal toxicity and mercapturate pathway metabolites was observed. The rat is reported to be
particularly susceptible to the formation of nephrotoxic metabolites via this pathway. Taken together, the data
presented here and the literature support the hypothesis that sotorasib-related renal toxicity is mediated by a
toxic metabolite derived from the mercapturate and B-lyase pathway. Our understanding of the etiology of the rat
specific renal toxicity informs the translational risk assessment for patients.

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A New Safety Concern for Glaucoma Treatment Demonstrated by Mass Spectrometry Imaging of Benzalkonium Chloride Distribution in the Eye, an Experimental Study in Rabbits

 

We investigated in a rabbit model, the eye distribution of topically instilled benzalkonium (BAK) chloride a commonly used preservative in eye drops using mass spectrometry imaging. Three groups of three New Zealand rabbits each were used: a control one without instillation, one receiving 0.01%BAK twice a day for 5 months and one with 0.2%BAK one drop a day for 1 month. After sacrifice, eyes were embedded and frozen in tragacanth gum. Serial cryosections were alternately deposited on glass slides for histological (hematoxylin-eosin staining) and immunohistological controls (CD45, RLA-DR and vimentin
for inflammatory cell infiltration as well as vimentin for Mu¨ller glial cell activation) and ITO or stainless steel plates for MSI experiments using Matrix-assisted laser desorption ionization time-of-flight. The MSI results were confirmed by a roundrobin study on several adjacent sections conducted in two different laboratories using different sample preparation methods, mass spectrometers and data analysis softwares. BAK was shown to penetrate healthy eyes even after a short
duration and was not only detected on the ocular surface structures, but also in deeper tissues, especially in sensitive areas involved in glaucoma pathophysiology, such as the trabecular meshwork and the optic nerve areas, as confirmed by images with histological stainings. CD45-, RLA-DR- and vimentin-positive cells increased in treated eyes. Vimentin was found only in the inner layer of retina in normal eyes and increased in all retinal layers in treated eyes, confirming an activation response to a cell stress. This ocular toxicological study confirms the presence of BAK preservative in ocular surface structures as well
as in deeper structures involved in glaucoma disease. The inflammatory cell infiltration and Mu¨ller glial cell activation confirmed the deleterious effect of BAK. Although these results were obtained in animals, they highlight the importance of the safety-first principle for the treatment of glaucoma patients.

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Multimodal stratification of predictive biomarker in lung cancer: A focus on immune checkpoint inhibitor

 

Dive into the complex landscape of immune checkpoint inhibitors (ICIs) in lung cancer in our poster presentation. 
 
As the use of immunotherapy in early-stage non-small cell lung cancer (NSCLC) remains a challenge, we offer a spatially-informed approach to identify useful biomarkers. By using spatial biomarker assays, and analysis involving spatial transcriptomics and proteomics, we reveal the cell-to-cell interactions in the tumor microenvironment.  
 
Download our poster to explore our findings and gain insights into the suitability of ICIs for personalized therapy

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Spatial distribution of B cells and lymphocyte clusters for the treatment of non-small cell lung cancer

 

Explore the spatial organization of tertiary lymphoid structures (TLS) in non-small cell lung cancer (NSCLC) and its impact on ant-PD-1 treatment response in our poster presentation.  
 
Using high-plex imaging mass cytometry staining, we investigated the relationship between TLS spatial organization, the tumor microenvironment, and patient response to therapy. We leveraged deep learning for cell segmentation and characterization to identify that the presence of tumor-associated TLS correlates with a positive response to ant-PD-1 therapy.  
 
Download our poster to dive into this spatial distribution insight and its potential impact on immunotherapies.

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Highly sensitive analysis using EVOSEP-LC-MS/MS assay for targeted PD-L1 and PD-1 expression level for predicting response to immune checkpoint inhibitors

 

Explore our recent poster presentation, which dives into a highly sensitive analysis using an EVOSEP-LC-MS/MS assay, with a focus on targeted PD-L1 and PD-1 expression levels to predict responses to immune checkpoint inhibitors (ICIs). 
 
We address the limitations of traditional PD-L1 and PD-1 immunoassays and their uncertain clinical value across tumor types. Through analysis of our robust method against routine immunoassays, and use of Overall Response Rate (ORR), we offer a new perspective on the predictive power of biomarkers for non-small cell lung cancer (NSCLC) therapy.  
 
Download our poster to discover the potential of this innovative approach.  

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LC/MS/MS VS. LC/HRMS: Identifying and quantifying oligonucleotides 

 

LC/MS/MS and LC/HRMS are formidable instruments employed in mass spectrometry for the identification and quantification of Oligonucleotides (OGNTs). Utilizing these approaches, drug developers can obtain detailed insights into the composition and structure of molecules for biotechnology and pharmaceuticals.

Considerations for choosing the right approach for your drug development project will depend on: 

  • What instrument you have 
  • Where you want to go 
  • How much information you want to collect in a single injection 

Discover which technique is best for you.

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Optimizing small molecule drug development strategies: A step by step approach to a rugged method


Creating a rugged method for the development of small molecule drugs is crucial in the quest for successful therapies. A systematic approach not only guarantees data consistency and reliability but also empowers you to make well-informed decisions, ultimately boosting project efficiency and success.

To help you navigate the complexities and uncertainties that come with advancing small molecules for drug development, we’ve outlined a robust strategy that includes 7 crucial steps.

Download our fact sheet to learn more.

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