Incendia Therapeutics’ Post

This week at #ASCO2024 we will be presenting two posters focused on applying AI-powered pathology for #cancerresearch. Read more about the abstracts and add the posters to your program. 𝘑𝘶𝘯𝘦 2𝘯𝘥, 2024 - 9:00 𝘈𝘔 - 12:00 𝘗𝘔 𝗔𝗯𝘀𝘁𝗿𝗮𝗰𝘁 𝟰𝟱𝟭𝟵: 𝗔𝘀𝘀𝗼𝗰𝗶𝗮𝘁𝗶𝗼𝗻 𝗼𝗳 𝗺𝗮𝗰𝗵𝗶𝗻𝗲 𝗹𝗲𝗮𝗿𝗻𝗶𝗻𝗴 (𝗠𝗟)–𝗱𝗲𝗿𝗶𝘃𝗲𝗱 𝗵𝗶𝘀𝘁𝗼𝗹𝗼𝗴𝗶𝗰𝗮𝗹 𝗳𝗲𝗮𝘁𝘂𝗿𝗲𝘀 𝘄𝗶𝘁𝗵 𝘁𝗿𝗮𝗻𝘀𝗰𝗿𝗶𝗽𝘁𝗼𝗺𝗶𝗰 𝗺𝗼𝗹𝗲𝗰𝘂𝗹𝗮𝗿 𝘀𝘂𝗯𝘁𝘆𝗽𝗲𝘀 𝗶𝗻 𝗮𝗱𝘃𝗮𝗻𝗰𝗲𝗱 𝗿𝗲𝗻𝗮𝗹 𝗰𝗲𝗹𝗹 𝗰𝗮𝗿𝗰𝗶𝗻𝗼𝗺𝗮 (𝗥𝗖𝗖) Presented by: Shima Nofallah Previously, transcriptomic analysis in the Phase 3 IMmotion 151 (Im151) trial identified 7 molecular subtypes that showed differential outcomes to Atezolizumab+Bevacizumab (A+B) vs Sunitinib (S) treatment. In this abstract, in collaboration with Genentech, human interpretable features (HIFs), including blood vessels, immune cells, fibroblasts, tissue morphologies, and nucleus shape, extracted from H&E-stained whole slide images (WSI) from Im151 and Im150, were used to identify positively associated HIFs within each subgroup in the Im151 WSI and then validated in Im150 molecular subgroups. 169 HIFs were differentially enriched across 3 molecular subsets in both datasets. Our results suggest that clinically relevant RCC subtypes may be extracted directly from H&E-stained WSI and may complement gene expression-based patient stratification and selection strategies. Add to your schedule: https://lnkd.in/eK4sSdxw 𝘑𝘶𝘯𝘦 3𝘳𝘥, 2024 - 1:30 𝘗𝘔 - 4:30 𝘗𝘔 𝗔𝗯𝘀𝘁𝗿𝗮𝗰𝘁 𝟴𝟱𝟯𝟵: 𝗖𝗼𝗿𝗿𝗲𝗹𝗮𝘁𝗶𝗼𝗻 𝗼𝗳 𝗶𝗺𝗺𝘂𝗻𝗲 𝗽𝗵𝗲𝗻𝗼𝘁𝘆𝗽𝗲𝘀 𝗱𝗲𝗿𝗶𝘃𝗲𝗱 𝗳𝗿𝗼𝗺 𝗛&𝗘-𝘀𝘁𝗮𝗶𝗻𝗲𝗱 𝘄𝗵𝗼𝗹𝗲 𝘀𝗹𝗶𝗱𝗲 𝗶𝗺𝗮𝗴𝗲𝘀 𝘄𝗶𝘁𝗵 𝗽𝗿𝗼𝗴𝗻𝗼𝘀𝗶𝘀 𝗮𝗻𝗱 𝗿𝗲𝘀𝗽𝗼𝗻𝘀𝗲 𝘁𝗼 𝗰𝗵𝗲𝗰𝗸𝗽𝗼𝗶𝗻𝘁 𝗶𝗻𝗵𝗶𝗯𝗶𝘁𝗼𝗿𝘀 𝗶𝗻 𝗡𝗦𝗖𝗟𝗖 Presented by: Bahar Rahsepar, PhD  The classification of tumors as inflamed, excluded or desert based on spatial patterns of tumor infiltrating lymphocytes (TILs) is a potential biomarker of patients likely to respond to checkpoint inhibitors (CPI).  In this abstract, in collaboration with Incendia Therapeutics, PathExplore IOP is used to classify immune-phenotype (IP) based on patch level TIL distribution in tumor core and periphery from H&E images. Survival analysis indicates Immune inflamed phenotype is associated with improved PFS in CPI-treated NSCLC patients independent of PD-L1 status. Add to your schedule: https://lnkd.in/eUZvYYzw #pathology #biotech #AI #digitalpathology #oncology #biotechnology #ASCO #ASCO24

If you're at #ASCO24, come check out Incendia Therapeutics' poster (Abstract 8539, Board 403) with PathAI on the the development of a new #AI-based method for immune phenotyping from H&E images and how hot/cold/excluded phenotypes relate to check-point inhibitor response in NSCLC. Title: Correlation of immune phenotypes derived from H&E-stained whole slide images with prognosis and response to checkpoint inhibitors in NSCLC Presenting Authors: Bahar Rahsepar, PhD, Senior AI Product Manager at PathAI and Laura Dillon, Ph.D., Vice President of Translational Medicine & Bioinformatics at Incendia Therapeutics Poster Session: Lung Cancer—Non-Small Cell Metastatic Date and Time: Monday, June 3 from 1:30 - 4:30 PM CDT (2:30 – 5:30 PM EDT) #TumorMicroenvironment #TME #NSCLC #ImmuneExclusion #PrecisionOncology

📃Scientific paper: Hypoxia-regulated carbonic anhydrase IX (CAIX) protein is an independent prognostic indicator in triple negative breast cancer Abstract: BACKGROUND: The effect of extracellular microenvironment (hypoxia and pH) has been regarded as a key hallmark in cancer progression. The study aims to investigate the effects of carbonic anhydrase IX (CAIX), a key hypoxia-inducible marker, in triple-negative breast cancer (TNBC) in correlation with clinicopathological parameters and predicting survival outcomes. METHODS: A total of 323 TNBC cases diagnosed at the Department of Anatomical Pathology, Singapore General Hospital from 2003 to 2013 were used. Immunohistochemical staining (IHC) was performed using CAIX antibody and digital mRNA quantification was performed using NanoString assays. CAIX membranous expression was correlated with clinicopathological parameters using Chi-squared test or Fisher’s exact tests. Disease-free survival (DFS) and overall-survival (OS) were estimated using Kaplan–Meier analysis and compared between groups with the log-rank test. RESULTS: Forty percent of TNBCs were observed to express CAIX protein and demonstrated significant association with larger tumour size (P = 0.002), higher histological grade (P < 0.001), and significantly worse disease-free survival (DFS) and overall survival (OS) (after adjustment: HR = 2.99, 95% CI = 1.78–5.02, P < 0.001 and HR = 2.56, 95% CI = 1.41–4.65, P = 0.002, respectively). Gene ontology enrichment analysis revealed six significantly enriched cellular functions (secretion, cellular component disassembly, regulation of protein complex assembly, glycolyt... Continued on ES/IODE ➡️ https://etcse.fr/BLr ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.

“The majority of oncogenic drivers are intracellular proteins, constraining their immunotherapeutic targeting to mutated peptides (neoantigens) presented by individual human leukocyte antigen (HLA) allotypes1. However, most cancers have a modest mutational burden that is insufficient for generating responses using neoantigen-based therapies. Neuroblastoma is a paediatric cancer that harbours few mutations and is instead driven by epigenetically deregulated transcriptional networks. Here we show that the neuroblastoma immunopeptidome is enriched with peptides derived from proteins essential for tumorigenesis. We focused on targeting the unmutated peptide QYNPIRTTF discovered on HLA-A*24:02, which is derived from the neuroblastoma-dependency gene and master transcriptional regulator PHOX2B. To target QYNPIRTTF, we developed peptide-centric chimeric antigen receptors (PC-CARs) through a counter panning strategy using predicted potentially cross-reactive peptides. We further proposed that PC-CARs can recognize peptides on additional HLA allotypes when presenting a similar overall molecular surface. Informed by our computational modelling results, we show that PHOX2B PC-CARs also recognize QYNPIRTTF presented by HLA-A*23:01, the most common non-A2 allele in people with African ancestry. Finally, we demonstrate potent and specific killing of neuroblastoma cells expressing these HLAs in vitro and complete tumour regression in mice. These data suggest that PC-CARs have the potential to expand the pool of immunotherapeutic targets to include non-immunogenic intracellular oncoproteins and allow targeting through additional HLA allotypes in a clinical setting.” Interesting new approach to the design of chimeric antigen receptors which allows for targeting of intracellular oncoproteins, by Mark Yarmarkovich, PhD Quinlen Marshall John Maris and larger team https://lnkd.in/ehurK939

Excited to unveil our lab's TOP-11 2023 research articles in breast cancer Check out the thread below for the highlights! A big thank you to our collaborators worldwide! Hospital Clínic de Barcelona Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) Universitat de Barcelona REVEAL GENOMICS, S.L.IOB Institute of Oncology Barcelona Num1 Tolaney et al., Lancet Oncol APT 10-year and HER2DX HER2DX risk score was significantly associated with invasive disease-free survival (hazard ratio [HR] per 10-unit increment 1·24 [95% CI 1·00–1·52]; p=0·047) and recurrence-free interval (1·45 [1·09–1·93]; p=0·011) https://shorturl.at/oAEQW The Lancet Num2 Waks et al., JAMA Oncol HER2DX in DAPHNe The HER2DX pCR score was significantly associated with pCR (odds ratio, 1.05; P < .001). The pCR rates in the HER2DX high, medium, and low pCR score groups were 92.6%, 63.6%, and 29.0%, respectively (high vs low odds ratio, 30.6; P < .001)." https://shorturl.at/ekEG8 JAMA Oncology Num3 Bueno-Muiño et al., JAMA Oncol HER2DX in GOM The assay-reported pCR score (as a continuous variable from 0-100) showed a statistically significant association with pCR (odds ratio [OR] per 10-unit increase, 1.43; P < .001). The pCR rates in the assay-reported pCR-high and pCR-low groups were 75.0% and 28.3%, respectively (OR, 7.85; 95% CI, 2.67-24.91; P < .001). A statistically significant interaction between the assay-reported pCR score and the effect of pertuzumab in pCR was observed. https://shorturl.at/iADO9 JAMA Oncology Num4 Prat et al., Nature Communications -- New applications for ctDNA We demonstrate that machine learning multi-gene signatures, obtained from ctDNA, identify complex biological features, including measures of tumor proliferation and estrogen receptor signaling, similar to what is accomplished using direct tumor tissue DNA or RNA profiling. https://lnkd.in/dXTx9Yfg Nature Portfolio Num5 Prat et al., Clinical Cancer Res -- Subtype in MBC HR+/HER2- The luminal A subtype had the best OS outcomes in both arms, while basal-like had the worst. Patients with HER2E (HR, 0.60; P=.018), luminal B (HR, 0.69; P=.023), and luminal A (HR, 0.75; P=.021) subtypes derived OS benefit with ribociclib. Patients with basal-like subtype did not derive benefit from ribociclib (HR, 1.92; P=.137) https://shorturl.at/abrv4 Num6 Brasó-Maristany et al. JNCI -- HER2DX vs TDM1 https://shorturl.at/irx12 Num7 Dieci et al. JNCI -- Patterns of relapse in HER2+ https://shorturl.at/dptK7 Num8 Villacampa et al. European J Cancer -- Treatments in HER2+ https://shorturl.at/krtB1 Num9 Fernandez et al. JAMA Oncology -- TILs vs B-cell signatures in HER2+ https://shorturl.at/kvyMN Num10 Weiss et al. Cancer -- Nodal positivity in HER2+ https://shorturl.at/xBGP0 Num11 Villacampa et al. Annals of Oncology -- HER2DX pCR score meta-analysis https://shorturl.at/gACGN

Microglia help limit the progression of Alzheimer’s disease (AD) by constraining amyloid-β (Aβ) pathology, effected through a balance of activating and inhibitory intracellular signals delivered by distinct cell surface receptors. Human leukocyte Ig-like receptor B4 (LILRB4) is an inhibitory receptor of the immunoglobulin (Ig) superfamily that is expressed on myeloid cells and recognizes apolipoprotein E (ApoE) among other ligands. Here, we find that LILRB4 is highly expressed in the microglia of patients with AD. Using mice that accumulate Aβ and carry a transgene encompassing a portion of the LILR region that includes LILRB4, we corroborated abundant LILRB4 expression in microglia wrapping around Aβ plaques. Systemic treatment of these mice with an anti-human LILRB4 monoclonal antibody (mAb) reduced Aβ load, mitigated some Aβ-related behavioral abnormalities, enhanced microglia activity, and attenuated expression of interferon-induced genes. In vitro binding experiments established that human LILRB4 binds both human and mouse ApoE and that anti-human LILRB4 mAb blocks such interaction. In silico modeling, biochemical, and mutagenesis analyses identified a loop between the two extracellular Ig domains of LILRB4 required for interaction with mouse ApoE and further indicated that anti-LILRB4 mAb may block LILRB4-mApoE by directly binding this loop. Thus, targeting LILRB4 may be a potential therapeutic avenue for AD. https://lnkd.in/eih8_YA9

🚀 Exciting News! 🚀 I am thrilled to share that my article "Recent Advances in Biosensor Technology for Early-Stage Detection of Hepatocellular Carcinoma-Specific Biomarkers: An Overview" has been published in the esteemed journal Diagnostics as part of the Special Issue on Recent Advancements of Molecular Biomarkers in Cancer. 🔗 Read the full article here: https://lnkd.in/grXUmZcg Hepatocellular carcinoma (HCC) is the most common liver malignancy, often resulting from pre-existing liver diseases like hepatitis and cirrhosis. Given its aggressive nature and poor prognosis, early detection is critical. However, conventional screening methods like radiological exams and biopsies have significant limitations. In this article, I explore the promising role of biosensors in revolutionizing early-stage detection of HCC. Biosensors offer a rapid, cost-effective, and accurate alternative, capable of detecting various biomarkers such as nucleic acids, proteins, and whole cells from a liquid biopsy. This technology holds immense potential to transform the landscape of HCC screening and diagnosis, offering a more accessible and less invasive option than traditional methods. Join me in delving into the advancements in biosensor technology and its future prospects in combating HCC. Your feedback and thoughts are highly appreciated! I would like to extend my heartfelt gratitude to my mentor, Dr. Naresh Mani, whose invaluable guidance and support made this research possible. His expertise and encouragement were instrumental in shaping this work, and I deeply appreciate his mentorship throughout this journey. #HepatocellularCarcinoma #Biosensors #EarlyDetection #CancerResearch #Diagnostics #MolecularBiomarkers #MedicalInnovation #HealthcareTechnology #ResearchPublication

#CARTcells vs #Bcells Deliver a 'Killer Punch' to #CAR-ve Onlookers 🥊 | #CARTcellTherapy activates CD8+ #Cytotoxic CARneg bystander #Tcells in non-Human Primates & Patients | New Study by Ulrike Gerdemann & Co. | CAR-T cells hold promise as a therapy for B-cell-derived malignancies, yet despite their impressive initial response rates, a significant proportion of patients ultimately experience relapse. While recent studies have explored the mechanisms of in vivo CAR-T cell function, little is understood about the activation of surrounding CARneg bystander T-cells and their potential to enhance tumor responses. We performed single-cell RNA-Seq (scRNA-Seq) on non-human primate (NHP) and patient-derived T-cells to identify the phenotypic and transcriptomic hallmarks of bystander activation of CARneg T-cells following B-cell targeted CAR-T cell therapy. Here* utilising a highly translatable CD20 CAR NHP model, the authors observed a distinct population of activated CD8+ CARneg T-cells emerging during CAR-T cell expansion. These bystander CD8+ CARneg T-cells exhibited a unique transcriptional signature with upregulation of NK-cell markers (KIR3DL2, CD160, KLRD1), chemokines and chemokine receptors (CCL5, XCL1, CCR9), and downregulation of naive T-cell-associated genes (SELL, CD28). A transcriptionally similar population was identified in patients following Tisagenlecleucel infusion. Mechanistic studies revealed that IL-2 and IL-15 exposure induced bystander-like CD8+ T-cells in a dose dependent manner. In vitro activated and patient-derived T-cells with the bystander phenotype efficiently killed leukemic cells through a TCR-independent mechanism. Collectively, this dataset provides the first comprehensive identification and profiling of CARneg bystander CD8+ T-cells following B-cell targeting CAR-T cell therapy and suggests a novel mechanism through which CAR-T cell infusion might trigger enhanced anti-leukemic responses. *https://lnkd.in/ec6HEsTK OPEN ACCESS preprint can be found at bioRxiv & medRxiv | https://lnkd.in/eTrfg2P8 | Celentyx Ltd #immunooncology #cytotoxicityassays www.celentyx.com Professor Nicholas Barnes PhD, FBPhS Omar Qureshi Catherine Brady

How would you like to diagnose lung cancer with just a breath and a urine test ❓❓🤔 That's the vision of a team of researchers from MIT Koch Institute for Integrative Cancer Research, led by Dr. Sangeeta Bhatia, Dr. Qian Zhong and Dr. Edward Tan who have developed a new technology that uses nanoparticle sensors to detect cancer-linked proteins in the lungs. 🔴 The sensors can be delivered by an inhaler or a nebulizer, and they produce a signal that accumulates in the urine, where it can be detected with a simple paper test strip. 💡 🔴 This technology could potentially replace or supplement the current gold standard for diagnosing lung cancer, low-dose CT. 🔴 It could have an especially significant impact in low- and middle-income countries that don't have widespread availability of CT scanners. 🌎 🔴 The researchers have tested their diagnostic system in mice that are genetically engineered to develop lung tumors similar to those seen in humans. 🔴 They found that the system could accurately detect early-stage lung tumors, using a combination of four sensors that target different proteases, which are enzymes that are often overactive in tumors. 🔬 🔴 The researchers plan to analyze human biopsy samples to see if the sensor panels they are using would also work to detect human cancers. In the longer term, they hope to perform clinical trials in human patients. 🔴 A company called Sunbird Bio has already run phase 1 trials on a similar sensor developed by the same lab, for use in diagnosing liver cancer and a form of hepatitis known as nonalcoholic steatohepatitis (NASH). 🚀 This research is a game-changer for early detection and treatment of lung cancer, which is the leading cause of cancer death worldwide. 🙌 If you found this post interesting and informative, don't forget to like it. 😉 Link to the full paper is below. https://lnkd.in/dkcPK4ME Follow 👉 #currentresearch for more latest research updates #nanoparticles #lungcancer #MIT #innovation #healthcare #biotechnology #diagnostics #sensors #machinelearning #paperstrip #urinetest #breath #inhaler #CTscan #breakthrough #currentresearch #engineering

Welcome to the world of biomarkers and translational biology. #BiomarkerDiscovery To start biomarkers are these molecules , that are like breadcrumbs in nature, guiding us through the complex pathways of health and disease. Whether it's DNA, proteins, or metabolites, biomarkers are the key to unlocking a treasure trove of insights about our bodies. #BiomarkerBreakthroughs translating these biomarkers into real-world impact. It's like transforming intricate research into practical tools for early diagnosis, treatment, and prevention. This journey from the lab bench to the bedside is where science truly shines. #FromBenchtoBedside Think about catching diseases at their earliest stages, thanks to biomarkers. By harnessing genomics, proteomics, and more, we're empowering doctors to predict, prevent, and personalize patient care. This is a game-changer for healthcare. #EarlyDetectionHeroes But let's be real – biomarker research isn't always smooth sailing. Challenges like validation, standardization, and ethical concerns are part of the journey. However, every adventure has its obstacles, and in the world of science, we thrive on overcoming them. #ScienceChallenges In the realm of cancer research, Take a look at the paper below – it reveals the potential of targeting oncogenic driver mutations like #KRAS. But, it also underscores the need for a holistic approach that's closer to biology, considering the complexity of the tumor microenvironment. And guess what? We're making strides in targeting tough-to-treat cancers, like #PDAC, using engineered #TCRT techniques. This involves triggering coordinated CD8+ and CD4+ responses that can thrive and combat the challenging tumor environment. This is where #syntheticbiology, exemplified by the #FAS_41BB switch, comes into play. HIGHLIGHTS: KRASG12D inhibition with MRTX1133 reverses early and advanced PDAC growth • MRTX1133 increases CD8+ T cells and reprograms cancer associated fibroblasts • Regression of advanced PDAC in response to MRTX1133 requires CD8+ T cells • KRASG12D inhibition induces FAS to facilitate CD8+ T cell mediated death #KRAS #precisiononcology #solidtumors #celltherapy #PDAC #patientsfirst https://lnkd.in/e2tCAhHV