This article and associated images are based on a poster originally authored by Irma O’Meara, Caitlin Shaw, Ana-Maria Nastase, Lauren Toms, Grace Haydon, Robert Pedley, Mohamed Naeem Khan, Talat Nahid Khan, Michael Eyres, Philip Auckland, Bruno Bellina, Gayle Marshall, and Bridgeen Callan and presented at ELRIG Drug Discovery 2025 in affiliation with Medicines Discovery Catapult (MDC) and KLAS Therapeutics.
This poster is being hosted on this website in its raw form, without modifications. It has not undergone peer review but has been reviewed to meet AZoNetwork's editorial quality standards. The information contained is for informational purposes only and should not be considered validated by independent peer assessment.
KLAS-PDT assessment
Image Credit: Image courtesy of Irma O’Meara et al., in partnership with ELRIG (UK) Ltd.
KLAS-PDT biodistribution
Image Credit: Image courtesy of Irma O’Meara et al., in partnership with ELRIG (UK) Ltd.
To assess the in situ biodistribution of KLAS-PDT, MDC developed a workflow that integrated MSI and fluorescence microscopy for the identification of KLAS-PDT in preclinical models of melanoma. An algorithm developed during the data processing step enabled data integration, identification, and quantification of the KLAS-PDT therapeutic. Accumulation of KT-001 was observed from the five-minute time point using both IT and IV route.
KLAS-PDT activation- Lipid oxidation
Image Credit: Image courtesy of Irma O’Meara et al., in partnership with ELRIG (UK) Ltd.
Source: ELRIG (UK) Ltd.
| Position of unsaturation |
Fatty acid chain |
MW |
[M-H] |
| C20:4n6 |
Arachidonic acid |
304.2402 |
303.2330 |
| C20:4;O |
Hydroxy Arachidonic Acid (20-HETE) |
320.2351 |
319.2279 |
| C20:4;O2 |
Arachidonic acid 5-hydroperoxide (5-HpETE) |
336.2300 |
335.2228 |
| C18:2n6 |
Linoleic acid |
280.2402 |
279.2330 |
| C18:2;O |
Hydroxy linoleic acid (9-HODE) |
296.2351 |
295.2279 |
| C18:2;O2 |
Dihydroxy linoleic acid (9S-HpODE) |
312.2300 |
311.2228 |
| C22:6n3 |
Docosahexaenoic acid (DHA) |
328.2402 |
327.2330 |
| C20:5n3 |
Eicosapentaenoic acid (EPA) |
302.2245 |
301.2173 |
| C20:5;O |
Hydroxy-EPA (20-HEPE) |
318.2194 |
317.2122 |
| C20:5;O2 |
Dihydroxy-EPA (5S-HpEPE) |
334.2144 |
333.2071 |
| C22:5n3 |
Docosapentaenoi c acid (DPA) |
330.2558 |
329.2486 |
Spatial distribution of arachidonic acid (AA) and its oxidized product hydroxy arachidonic acid (HETE). The distribution or AA matches the areas with remaining skin structure whereas HETE is localized in close proximity to regions with Rose Bengal. Similarly, other oxidized fatty acid species (shown in the table above), such as hydroxyl linoleic acid, hydroxy EPA, and dihydroxy EPA, were also detected with a similar distribution as HETE.
The detection of these species could be explained by the peroxidation of the fatty acid species pathway, where hydroxy fatty acid species are produced from the presence of reactive oxygen species (ROS), possibly derived from the activation of KLAS-PDT. All ions were putatively assigned according to their exact masses.
KLAS-PDT activation- Mitochondria imaging
Image Credit: Image courtesy of Irma O’Meara et al., in partnership with ELRIG (UK) Ltd.
*Rose Bengal- Photosensitiser, TOM20- mitochondria, DAPI- nucleus
Representative airyscan images of mitochondria in malignant melanoma tissue sections following KLAS-PDT dosing with and without phototherapy, as well as a samples dosed with PBS used as a control + phototherapy. The signal intensity from the mitochondria seems to decrease in areas where rose bengal from the KLAS-PDT compound was present.
KLAS-PDT activation- Transcriptomic changes
Image Credit: Image courtesy of Irma O’Meara et al., in partnership with ELRIG (UK) Ltd.
Selection of regions of interest (ROIs) based on the presence of the rose bengal (RB+, RB-) and the region of tumor (surface or excision side).
Whole transcriptome analysis
Image Credit: Image courtesy of Irma O’Meara et al., in partnership with ELRIG (UK) Ltd.
Plot showing the t-SNE dimensional reduction of transcriptomic profiles from samples treated with KLASPDT with and without photoactivation or with PBS and photoactivation (controls).
Image Credit: Image courtesy of Irma O’Meara et al., in partnership with ELRIG (UK) Ltd.
Possible enriched pathways identified with DSP-protein analysis. The heatmap shows the average enrichment score for each treatment group. This analysis highlighted interleukin, TNF, and inflammation-associated pathways that were upregulated with treatment, as well as increased DNA damage repair, NO signaling, a decrease in matrix remodeling, and metastasis pathways in RB+ regions.
Single-cell spatial transcriptomics by Curio Seeker
Image Credit: Image courtesy of Irma O’Meara et al., in partnership with ELRIG (UK) Ltd.
Curio Seeker tiles comprise a monolayer of barcoded microparticles (beads) that contain poly(dT) sequences, allowing mRNA molecules from the tissue to hybridize. Gene expression is reconstructed spatially by using the bead barcode to map individual sequencing reads back to their original XY coordinate. This approach enables unbiased, spatial, whole-transcriptome profiling at single-cell resolution.
Conclusion
- MDC applied Spatial Biology to the analysis of preclinical melanoma models dosed with KLAS-PDT (non-activated and photoactivated).
- Accumulation of KLAS-PDT was observed from the five-minute time point using both IT and IV routes.
- High-resolution microscopy revealed the colocalization of KLAS-PDT with malignant melanocytes. The intensity from the mitochondrial staining seems to decrease where rose bengal was present.
- Molecular imaging revealed the possible presence of oxidized fatty acid species localized in close proximity to regions with photoactivated KLAS-PDT compound. These species could be derived from lipid peroxidation initiated by ROS.
- Spatial transcriptomics and proteomics analysis suggested that rose bengal-positive areas showed enriched immune and inflammation-associated pathways, including possible upregulation of immune activation markers.
- All together, these results underscore the transformative power of spatial biology in oncology drug development and set the stage for the advancement of KLAS-PDT towards clinical application.
About Medicines Discovery Catapult
Medicines Discovery Catapult (MDC) is a national UK life-sciences organisation dedicated to accelerating drug discovery and translating bold scientific ideas into real-world therapeutics.
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Last Updated: Nov 26, 2025