tbuckley/cabot-search huggingface dataset:
Abstract 5668: Preclinical efficacy of tumor treating fields (TTFields) for small cell lung carcinoma (SCLC)
Authors: Rotem Engelman, Lina Somri-Gannam, Talya Borkum, Roni Blatt, Daria Gerasimova, Shay Cahal, Catherine Tempel Brami, Mai Shai, Eyal Dor-On, Itai Tzchori, Adi Haber, Moshe Giladi, Yoram Palti
Journal: Cancer Research (2025)

Abstract Purpose: Small cell lung cancer (SCLC) is a highly aggressive malignant neoplasm, accounting for 10-15% of lung cancer cases, characterized by rapid growth, and early metastasis. The standard of care is combination chemotherapy with cisplatin or carboplatin plus etoposide, administered together with immunotherapy and concurrent chest radiotherapy. The current preclinical study aimed to investigate the efficacy of TTFields for treatment of SCLC and examine the effect of TTFields together with the standard-of-care chemotherapies. Methods: DMS-53 and H196 SCLC cells were treated with TTFields (1 V/cm RMS, 150 kHz, 72 h for DMS-53 cells; 1.62 V/cm RMS, 150 kHz, 120 h for H196 cells), alone or with the addition of different concentrations of cisplatin or etoposide. Efficacy was measured by analyzing cell count, colony formation, and apoptosis induction. The overall effect was calculated by multiplying cell count with colony formation. TTFields efficacy was further evaluated in vivo, in mice orthotopically inoculated with murine KP3 SCLC cells. 7 days after inoculation, TTFields or sham-heat were continuous applied for 9 days. Tumor volume was examined by magnetic resonance imaging (MRI) at treatment end. Results: TTFields reduced cell count, induced apoptosis, and provided an increased overall effect relative to control in both cell lines. Application of cisplatin or etoposide alongside TTFields showed a synergistic interaction in H196 cells, which was higher for the latter chemotherapy. In DMS-53 cells, the concomitant treatment of TTFields with either chemotherapy showed an additive interaction in cytotoxicity and a synergistic overall effect, which matched the relatively high levels of apoptosis in this cell line. Furthermore, TTFields significantly reduced tumor growth relative to control in the mouse model. Conclusions: Our results demonstrate efficacy for TTFields for the treatment of SCLC in preclinical models, and a potential advantage for TTFields concomitant with the standard-of-care chemotherapies for this malignancy. Future studies will test the effect of TTFields concomitant with both chemotherapies, in vitro and in vivo; and together with immunotherapy and chemotherapy. Citation Format: Rotem Engelman, Lina Somri-Gannam, Talya Borkum, Roni Blatt, Daria Gerasimova, Shay Cahal, Catherine Tempel Brami, Mai Shai, Eyal Dor-On, Itai Tzchori, Adi Haber, Moshe Giladi, Yoram Palti. Preclinical efficacy of tumor treating fields (TTFields) for small cell lung carcinoma (SCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5668.
Abstract 5656: Next-level efficiency: StraightFrom Spleen Isolation Kits - standardizing isolation of untouched B cells with minimal hands-on time
Authors: Sebastian Flade, Amelie Borczewski, Stefano Vergani, Gregor Winkels, Anna Baranska, Anne Richter
Journal: Cancer Research (2025)

The study of mouse B cells is essential for advancing our understanding of the immune system, developing new vaccines, and driving progress in immunotherapy through the discovery of new targets. Mouse B cells are abundant in the spleen, one of the major lymphoid organs, making splenic isolation a critical step in B cell research. General workflow to isolate these cells relies on manual mechanical disruption of the mouse spleen and subsequent magnetic purification. However, this combination of methods is time-consuming and operator dependent, with important implication for reproducibility and major impact on downstream application. To address this gap, we at Miltenyi have developed the StraightFromSpleen kit, an all-in-one solution for isolation of highly pure murine B cells from mouse spleen. Briefly, we used the GentleMACS dissociator to disrupt the spleen while labeling unwanted cells with an antibody cocktail. We then performed automated magnetic labeling of cells and isolation of untouched B cells and Pan B cells using the autoMACS NEO Separator. After separation, we measured purity, viability and yield and compared these results with those obtained using a standard isolation kit. Finally, we tested the functionality of the isolated B cells and Pan B cells by culturing then with LPS or in presence of anti-CD40 antibody and IL-4, to promote proliferation, IgG class-switch and differentiation to antibody secreting cells. We demonstrated that the newly developed StraigthFrom Spleen kits allow for isolation of highly viable and pure B cells. Isolated B cells efficiently proliferated in vitro, differentiate to CD138+ antibody secreting cells and were able to class-switch. In conclusion, we have developed a simple, fast, and reliable cell isolation method that significantly accelerates the isolation of functional B cells. This represents an attractive alternative to the laborious multi-step protocols commonly used in academic and industrial laboratories and has the potential to set a new standard for the B cell field. Citation Format: Sebastian Flade, Amelie Borczewski, Stefano Vergani, Gregor Winkels, Anna Baranska, Anne Richter. Next-level efficiency: StraightFrom Spleen Isolation Kits - standardizing isolation of untouched B cells with minimal hands-on time [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5656.
Abstract 5663: High-content screening platform for comprehensive profiling in drug discovery
Authors: Maciej B. Olszewski, Natalia Gostynska, Klaudia Lesniak, Alicja Martyniak, Magdalena Kieltyka
Journal: Cancer Research (2025)

A robust, multi-modal high-content screening (HCS) platform enables fast and quantitative assessment of cellular phenotypes over a variety of research applications. Our integrated system combines innovative imaging technologies, automated analysis, and cell profiling capabilities to drive drug discovery and biological research programs. Selvita HCS platform features multiparametric cellular phenotyping: simultaneous measurement of morphological, functional, and molecular cellular properties. The data is acquired by automated fluorescence microscopy: high-resolution imaging with multiplexed fluorescent markers. The images are then analyzed, as needed, by standard or machine learning-assisted image analysis. Advanced algorithms are used to accurately extract cellular features. This enables building various kinetic and endpoint assays: cell viability, apoptosis, proliferation, and subcellular localization studies, to name a few. The platform allows multiple application domains, including therapeutic target validation, mechanism of action studies, pharmacological screening and toxicity assessment. Validated across a variety of models under different experimental conditions, our HCS platform generates high-throughput data with high inter-assay consistency. The customizable protocols facilitate adaptable research support across programs in oncology, neuroscience, immunology, and metabolic disease. Examples of successful cases include: tissue analysis with automated identification of areas of interest and subsequent high-resolution rescanning, combined FISH / immunofluorescence studies in target validation, 100+ K compound screening campaign based on reporter cell line and protein-protein interaction study in DNA repair complex assembly, using proximity ligation assay. Future development will focus on expanding the machine learning capabilities, multiplexing potential, and integration of advanced computational biology tools to aid in the improvement of predictive cellular modeling. Citation Format: Maciej B. Olszewski, Natalia Gostynska, Klaudia Lesniak, Alicja Martyniak, Magdalena Kieltyka. High-content screening platform for comprehensive profiling in drug discovery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5663.
Abstract 5675: ThiOBI® platform, a novel hydrophilic linker for irreversible cysteine-selective biomolecular conjugation, demonstrated potent and durable antitumor activities in various animal models
Authors: Yu-Chao Huang, Ting-Wei Liu, Chi-Huan Lu, Ren-Yu Hsu, Nan-Hsuan Wang, Ya-Chi Chen, Ming-Tain Lai, Teng-Yi Huang
Journal: Cancer Research (2025)

Abstract The ThiOBI® platform represents a cutting-edge approach for the development of next-generation cysteine (Cys)-based drug conjugates including a wide range of cysteine-containing biomolecules, such as nanobodies, antibody fragments, and peptides. This platform leverages a novel hydrophilic stable linker that efficiently delivers the drug to the site of action to enhance therapeutic potential. In addition, an irreversible thiol conjugation enables Cys-selective biomolecular modification providing meticulous control of the drug conjugation process. Maleimide is a chemical group commonly used in the design of linkers for bio-conjugation, particularly in antibody-drug conjugates (ADCs), where it plays a key role in attaching a cytotoxic payload to the antibody through a linker. Seven FDA approved ADCs used Cys-maleimide chemistry. However, a major limitation of the traditional cysteine-maleimide conjugated ADCs is their instability due to retro-Michael deconjugation, which can lead to premature payload release in circulation. The ThiOBI® platform addresses this challenge by employing a stable hydrophilic linker to prevent such reaction ensuring drug delivery in a more controllable manner. This innovation profoundly improves stability and physicochemical properties of the conjugated biomolecules, minimizes off-target effects, and enhances the overall therapeutic index. In preclinical studies, ThiOBI®-based ADCs demonstrated potent and durable antitumor activities across a variety of animal models. Notably, the platform possesses substantial flexibility that is capable of incorporating a range of payloads and biomolecular formats, including antibody fragments, nanobodies, and peptides, all of which show enhanced therapeutic activity. This versatility allows for targeting a broader spectrum of cancers and diseases that are not easily addressed by conventional antibody-based ADCs. The promising preclinical results highlight the versatility and therapeutic promise of the ThiOBI® platform, positioning it as a powerful tool for the development of next-generation drug conjugates. The successful demonstration of potent and durable antitumor activities in animals provides a strong foundation for future clinical development of the biomolecules derived from ThiOBI®. Citation Format: Yu-Chao Huang, Ting-Wei Liu, Chi-Huan Lu, Ren-Yu Hsu, Nan-Hsuan Wang, Ya-Chi Chen, Ming-Tain Lai, Teng-Yi Huang. ThiOBI® platform, a novel hydrophilic linker for irreversible cysteine-selective biomolecular conjugation, demonstrated potent and durable antitumor activities in various animal models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5675.
Abstract 5306: Dissecting the formation mechanisms of tertiary lymphoid structures and their impact on prognosis and immunotherapy
Authors: Ben Liu, Wenbo Zhu, Mengyue Qiu, Yanxin Yao, Kexin Chen
Journal: Cancer Research (2025)

Abstract Background: The mortality from gastric cancer is high due to its frequently advanced stage at diagnosis. The standard treatment is mainly surgical, including a comprehensive treatment model of chemotherapy, radiotherapy, targeted therapy and immunotherapy. However, the existing classification of gastric cancer cannot fully guide the precise treatment. TLSs, sometimes also referred to as tertiary lymphoid organs or ectopic lymphoid structures, are organized aggregates of immune cells that arise postnatally in nonlymphoid tissues. The presence of TLSs in tumor environment often indicates a better prognosis. Method: Identifying the expression of TLSs and its maturation status on pathological sections of gastric cancer surgical specimens via HE staining, immunohistochemistry staining and multi-color fluorescence staining. Surgical tumor specimens were collected and analyzed using single-cell RNA sequencing and spatial single-cell transcriptomics sequencing. To identify TLSs artificially by establishing the artificial intelligence machine learning models of TLSs. To explore the mechanism of TLSs formation in the tumor environment in vivo by humanized PDOX mice and in vitro by co-culture systems of gastric organoids and immune cells. Results: HE staining, immunohistochemistry staining and multi-color fluorescence staining of tumor sections identified the expression and mature status of TLSs. Single-cell sequencing and spatial single-cell transcriptomics sequencing found the specific markers to identify the TLSs and analyzed the cell composition and cell communication in the tumor environment. Artificial intelligence machine learning models of TLSs identified the presence of TLSs and its maturation status. Furthermore, in vitro co-culture systems of organoids and immune cells and humanized PDOX mice found that organoids of patients with high TLSs score increased apoptosis of tumor cells while using PD-1 antibody and CTLA-4 antibody. Conclusions: The high expression of mature TLSs indicates a better survival. We establish the artificial intelligence machine learning models of TLSs to identify the presence of TLSs and its mature status. We establish the TLS score to predict the TLS expression and prognosis of patients. Patients with high TLSs score have a better survival and are more sensitive to PD-1 antibody and CTLA-4 antibody. Citation Format: Ben Liu, Wenbo Zhu, Mengyue Qiu, Yanxin Yao, Kexin Chen. Dissecting the formation mechanisms of tertiary lymphoid structures and their impact on prognosis and immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5306.
Abstract 4535: Targeting YAP1 and DKK1 pathways to suppress peritoneal carcinomatosis in gastric adenocarcinoma
Authors: Yibo Fan, Shumei Song, Gengyi Zou, Longfei Huo, Ailing Scott, Ruiping Wang, Enyu Dai, Shan Shao, Linghua Wang, Shilpa Dhar, Jaffer Ajani
Journal: Cancer Research (2025)

Abstract Peritoneal carcinomatosis (PC), characterized by malignant ascites cells or implants, affects approximately 45% of advanced gastric adenocarcinoma (GAC) patients and is associated with a poor prognosis, with survival rates often less than six months. Despite its prevalence and severe impact, the molecular mechanisms underlying PC in GAC remain poorly understood, highlighting a significant unmet need for targeted therapies. Our previous studies demonstrated that YAP is highly expressed in PC cells, promoting cancer stem cell (CSC)-like properties and correlating with decreased patient survival. Here, we observed that high YAP1 expression is inversely correlated with CD8+ T cell infiltration in GAC. RNA sequencing analysis revealed a significant reduction in DKK1 expression upon YAP1 depletion, and both YAP and DKK1 were highly expressed in PC cells. High expression of these markers is significantly associated with poor survival outcomes in GAC patients. Further experiments showed that ectopic DKK1 expression in YAP1 knockout cells restored cell proliferation, tumor sphere formation, cell invasion, and impaired CD8+ T cell function. Dual inhibition of YAP and DKK1 markedly reduced tumor growth and enhanced CD8+ T cell responses within the TME. Combination therapy with YAP antisense oligonucleotides (ASO), DKN1 antibody, and anti-PD-1 further extended overall survival and bolstered immune response. Our findings reveal a critical role of YAP1 in maintaining an immunosuppressive microenvironment through DKK1 in GAC with PC. This combined inhibition approach holds promise and warrants further investigation as a therapeutic strategy for GAC patients with PC. Citation Format: Yibo Fan, Shumei Song, Gengyi Zou, Longfei Huo, Ailing Scott, Ruiping Wang, Enyu Dai, Shan Shao, Linghua Wang, Shilpa Dhar, Jaffer Ajani. Targeting YAP1 and DKK1 pathways to suppress peritoneal carcinomatosis in gastric adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4535.
Abstract 6328: Metformin induces cell cycle arrest and inhibits proliferation in <i>KRAS</i>-mutated colorectal cancer
Authors: Devanshi Patel, Michelle Pham, Parthiv Medidi, Holli Ann Loomans-Kropp
Journal: Cancer Research (2025)

Abstract Purpose: Our objective was to evaluate the potential of metformin for colorectal cancer (CRC) prevention. Methods: HT-29 (KRAS wild-type) and SW837 (KRAS G12D mutated) CRC cells were used for in vitro analyses. Cells were treated with 10mM (HT-29) or 2mM (SW837) metformin for up to 96 hours. Proliferation was assessed by raw cell counts, CellTiter 96 Aqueous Proliferation Assay, and 0.5% crystal violet staining. Propidium iodide staining was used to evaluate cell cycle and analyzed on a BD FACS Aria III. Experimental results were analyzed using Student’s t-test or Mann-Whitney U and expressed as the mean +/- standard deviation. Statistical analysis of in vitro experiments was performed in Prism 10.0 (GraphPad) and significance was set at p&amp;lt;0.05. Sequencing was completed using an Illumina NovaSeq X Plus (Novogene). Differential expression analysis was performed using DESeq2RPackage and enrichment analysis using clusterProfiler and GSEA for Go, KEGG, Reactome, DO, and DisGeNET. Statistical significance was set at an adjusted p&amp;lt;0.05. Results: We found that metformin treatment of CRC cells in vitro significantly reduced proliferation and cellular growth after 48 and 96 hours in SW837, but not HT-29 cells. Cell cycle analysis showed that SW837 metformin treatment increased the percent of cells in G1, suggesting G1 cell cycle arrest. Sequencing analysis of SW837 cells identified 2738 and 2492 genes significantly up- and downregulated with metformin treatment, respectively. The top significantly differentially regulated genes were ATF3, SNAI2, UPP1, GDF15, and SLC20A1. Gene ontology analysis of metformin-treated SW837 cells showed differentially regulated genes involved in chromosome segregation, DNA replication, and cell cycle checkpoint, supporting our findings. Independent validation of top hits and key genes in pathways of interest, including CDC42, BRIP1, EME1, and POLE2, is ongoing. Conclusions: Treatment of KRAS-mutated CRC cells with metformin significantly reduced cell proliferation and induced cell cycle arrest. Sequencing analysis showed significant regulation of cell cycle and proliferation-associated pathways, supporting our observed phenotype and providing insight into previously unidentified pathways regulated by metformin. The results from this study may have implications for the future use of metformin for CRC prevention. Citation Format: Devanshi Patel, Michelle Pham, Parthiv Medidi, Holli Ann Loomans-Kropp. Metformin induces cell cycle arrest and inhibits proliferation in KRAS-mutated colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6328.
Abstract 3759: Single cell transcriptomics on a bioprinted 3D neurovascular unit glioblastoma model identifies pharmacological interventions that selectively target tumor cells
Authors: Yen-Ting Tung, Min Jae Song, Marc Ferrer
Journal: Cancer Research (2025)

Abstract The tumor microenvironment (TME) is the cellular environment in which cancer cell exist and is made up of a combination of stroma cells and extra cellular matrix (ECM), secreted biomolecules, including cytokines, from both stroma cells and tumor cells. The TME composition drives tumor growth and drug resistance. We previously established a 96-wells based bioprinted glioblastoma (GBM) model that includes a neurovascular unit (NVU) made up of endothelial cells, astrocytes and pericytes. We demonstrated its applicability for drug screening by using high content imaging system to measure tumor size and vascular integrity. We then performed single cell RNA sequencing on this bioprinted NVU-GBM model. We used the single cell transcriptomics data to investigate ligand-receptor interactions between stroma and GBM cells, to find molecular pathways that potentially drive tumor growth and be targets for pharmacological intervention as anticancer drugs. We identified 50 ligand-receptors pairs and selected those with genes exclusively expressed in GBM cells but not in the stroma cells, to minimize potential toxic effects of drugs to the non-cancer cells. We performed a drug screen of 34 compounds targeting many of these receptors on the GBM cells, and identified 15 compounds that reduced GBM cells growth, with minimal effects on vascular integrity. This result demonstrates a promising pharmacogenomics approach to using bioengineered tumor growth tissue models that include the TME, integrated with single cell transcriptomics, to find actionable pharmacological targets that inhibit tumor growth without affecting the stroma cells. Citation Format: Yen-Ting Tung, Min Jae Song, Marc Ferrer. Single cell transcriptomics on a bioprinted 3D neurovascular unit glioblastoma model identifies pharmacological interventions that selectively target tumor cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3759.