tbuckley/cabot-search huggingface dataset:
Abstract 1992: Detection rate for <i>ESR1</i> mutations is higher in CTC-derived genomic DNA than in paired plasma cfDNA samples as revealed by ddPCR
Authors: Stavroula Smilkou, Aliki Ntzifa, Victoria Tserpeli, Ioanna Balgkouranidou, Alkistis Papatheodoridi, Evangelia Razis, Helena Linardou, Christos Papadimitriou, Amanda Psyrri, Flora Zagouri, Stylianos Kakolyris, Evi Lianidou
Journal: Cancer Research (2025)

Abstract Plasma cell-free DNA (cfDNA) analysis to track estrogen receptor 1 (ESR1) mutations is highly beneficial for the identification of tumor molecular dynamics and the improvement of personalized treatments for patients with metastatic breast cancer (MBC). Plasma cfDNA is, up to now, the most frequent liquid biopsy analyte used to evaluate ESR1 mutational status. Circulating tumor cell (CTC) enumeration and molecular characterization analysis provides important clinical information in patients with MBC. In this study, we investigated whether analysis of CTCs and circulating tumor DNA (ctDNA) provide similar or complementary information for the analysis of ESR1 mutations. We analyzed both plasma cfDNA (n=90) and paired CTC-derived genomic DNA (gDNA; n=42) from 90 MBC patients for seven ESR1 mutations. Eight out of 90 (8.9%) plasma cfDNA samples tested using the ddPLEX Mutation Detection Assay (Bio-Rad), were found positive for one ESR1 mutation, whereas 11/42 (26.2%) CTC-derived gDNA samples were found positive for at least one ESR1 mutation. Direct comparison of paired samples (n=42) revealed that the ESR1 mutation rate was higher in CTC-derived gDNA (11/42, 26.2%) than in plasma cfDNA (6/42, 14.3%) samples. Our results, using this highly sensitive ddPLEX assay, reveal a higher percentage of mutations in CTC-derived gDNAs than in paired ctDNA in patients with MBC. CTC-derived gDNA analysis should be further evaluated as an important and complementary tool to ctDNA for identifying patients with ESR1 mutations and for guiding individualized therapy. Citation Format: Stavroula Smilkou, Aliki Ntzifa, Victoria Tserpeli, Ioanna Balgkouranidou, Alkistis Papatheodoridi, Evangelia Razis, Helena Linardou, Christos Papadimitriou, Amanda Psyrri, Flora Zagouri, Stylianos Kakolyris, Evi Lianidou. Detection rate for ESR1 mutations is higher in CTC-derived genomic DNA than in paired plasma cfDNA samples as revealed by ddPCR [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 1992.
Abstract 5270: Novel dual-stain IHC assay enables discovery with enhanced clarity
Authors: Scott Anderson, Stephen Pyper, Jack Heath, Julio Poveda
Journal: Cancer Research (2025)

Abstract Background: Immunohistochemistry (IHC) analysis has become a powerful and integral component in the diagnostic workup of tumors. It has been essential in biomarker discovery, with a growing demand for high-output methods that maximize data from limited tissue samples. Chromoplex II, an advanced technique that enables the simultaneous detection of dual stains on a single slide, permits the selection of primary antibodies to be stained in either color, aiding tissue differentiation while minimizing the interference often seen with endogenous pigments or slide debris. The duplex approach also reduces slide usage compared to single-stains and individual slides. Methods: Using the BOND-III Automated IHC and in-situ hybridization (ISH) stainer from Leica Biosystems, Chromoplex II was evaluated in three dual-marker applications. At least five cases with known tumors of distinct tumor histology/classification were utilized to examine differences between the distinct cellular histology (i.e., adenocarcinoma and squamous carcinoma) as well as classical Hodgkin lymphoma (cHL) versus nodular lymphocyte predominant Hodgkin lymphoma (NLP). Another commonly encountered scenario is the difficulty in separating lung adenocarcinoma and bystander macrophages, so these tissues were tested as well. Stained slides were scanned using the Aperio GT 450 scanner from Leica Biosystems and evaluated by a clinical pathologist for specificity and comparability to single staining. The marker combinations and tissues tested were the following: CD20/CD30: Lymph node CK5/Napsin A: Lung CD163/PD-L1: Lung Results: In all three marker combinations, the Chromoplex II kit produced distinct red and green stains, providing a clear visualization of target markers. Importantly, it minimized background interference, significantly enhancing clarity in challenging tissue sections. The slides exhibited comparable signal and reproducibility compared to single marker staining, and many examples were noted in which the dual stain provided vital context about the nature of the relationship between the two markers studied. Conclusions: Chromoplex II represents a promising tool for high-throughput biomarker studies in research, offering benefits in both clarity of staining and operational efficiency by reducing slide volume. Furthermore, additional studies and/or combinations are necessary to explore expanded marker combinations for broader cancer biomarker research applications. Citation Format: Scott Anderson, Stephen Pyper, Jack Heath, Julio Poveda. Novel dual-stain IHC assay enables discovery with enhanced clarity [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 5270.
Abstract 5290: Spatial multi-omics defines a shared glioblastoma infiltrative signature at the resection margin
Authors: Balagopal Pai, Susana Ramos, Wan Sze Cheng, Tanvi Joshi, Gabrielle Price, Jessica Tome-Garcia, Kristin Beaumont, Robert Sebra, Raymund Yong, Elena Zaslavsky, Nadejda M. Tsankova
Journal: Cancer Research (2025)

Abstract Glioblastoma (GBM) remains an untreatable disease. Understanding of GBM’s infiltrative biology at the resection margin is limited, despite causing disease recurrence and progression. To address this, we generated a high-throughput single-nucleus (sn)RNA-seq and snATAC-seq multi-omic dataset from six tumors with distinct genomic drivers and combined it with spatial transcriptomics to characterize the unique molecular phenotype of GBM near the margin. By contrasting GBM-specific biology in matching “Core” vs. “Margin” dissections, we define unique, shared “GBM infiltration” and chromatin accessibility signatures near the margin. We prioritize EGFR as a top differentially expressed and accessible “Margin” marker across GBM subtypes, show its dynamic expression along a core-to-margin infiltration trajectory, and validate its role in migration through CRISPR/Cas9 deletion in two patient-derived models. ChIP-seq studies further corroborate preferential TEAD1 binding at EGFR’s accessible regulatory elements. This validated multi-omic dataset enables further studies into tumor and microenvironment biology in the context of residual GBM disease. Citation Format: Balagopal Pai, Susana Ramos, Wan Sze Cheng, Tanvi Joshi, Gabrielle Price, Jessica Tome-Garcia, Kristin Beaumont, Robert Sebra, Raymund Yong, Elena Zaslavsky, Nadejda M. Tsankova. Spatial multi-omics defines a shared glioblastoma infiltrative signature at the resection margin [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 5290.
Abstract 6083: A fully human agonistic antibody against a unique epitope on TREM1 demonstrates immune stimulatory activities both in vitro and in vivo
Authors: Lan Yang, Di Liu, Zhen Zhang, Yan Jiang, Qinghao Liu, Qian Shi
Journal: Cancer Research (2025)

Abstract Triggering receptor expressed on myeloid cells-1 (TREM1) is a proinflammatory receptor that amplifies immune responses. TREM1 is expressed on neutrophils, subsets of monocytes and tissue macrophages, and suppressive myeloid populations in the tumor microenvironment (TME), including tumor-associated neutrophils, monocytes, and tumor-associated macrophages. Stimulation by TREM1-mediated inflammatory signaling may promote an immunostimulatory TME and inhibit tumor growth. We developed DX002, a fully human agonistic anti-TREM1 monoclonal antibody. DX002 binds to a unique epitope and has low internalization property. Deep mutational scanning (DMS) of the human TREM1 antigen was applied to map DX002 binding epitope and result showed that DX002 was a ligand-competitive agonist that mimic the function of ligand PGLYRP1 protein. In vitro, Plate-bound DX002 up-regulates the expression of costimulatory molecules on monocytes and induces the production of proinflammatory cytokines. Moreover, soluble DX002 also induces the production of proinflammatory cytokines in PBMCs. In vivo, DX002 exhibits significant tumor growth inhibition activity in MC38 syngeneic model in human TREM1 transgenic mice. Taken together, the TREM1 agonistic antibody DX002 is shown to be active both in vitro and in vivo. Citation Format: Lan Yang, Di Liu, Zhen Zhang, Yan Jiang, Qinghao Liu, Qian Shi. A fully human agonistic antibody against a unique epitope on TREM1 demonstrates immune stimulatory activities both in vitro and in vivo [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 6083.
Abstract 6085: Engineered anti-CD40 agonist antibody as a novel cancer neoantigen vaccine carrier
Authors: Dahee Jung, Xiaoying Cai, Wonkyung Oh, Seung-Oe Lim, Steve Lee
Journal: Cancer Research (2025)

Abstract Somatic mutations in cancer cells lead to the expression of neoantigens that can be targeted by personalized vaccines utilizing patient’s own host immune system to fight against cancer. However, current personalized cancer vaccines have shown poor clinical outcomes due to the lack of effective delivery methods. To address the issues, our study aims to develop a novel vaccine platform that targets dendritic cells (DCs) and delivers neoantigen peptides more effectively by an anti-CD40 agonistic antibody expressing monovalent streptavidins (αCD40-mSAs). The agonistic anti-CD40 antibody will target and activate DCs, and the mSA compartment will allow the easy and fast loading of two biotinylated payloads (e.g. peptides and RNAs) on each vaccine carrier. CHO cell-based recombinant protein production method was used to biosynthesize αCD40 and αCD40-mSAs. Cloning vectors were reconstructed using mouse IgG2a, incorporating peptide sequences from the anti-mouse CD40 agonist antibody (clone FGK45) and monovalent streptavidin. For the biophysical properties of produced αCD40-mSAs, Surface Plasmon Resonance (SPR) for mouse CD40 and fluorescence polarization for biotin binding of mSAs have been used. Biotin- ovalbumin (OVA) peptide loaded αCD40-mSAs were subcutaneously injected into the footpad of the mice, and the collected lymph nodes were imaged with confocal microscopy and checked subtype of immune cells using flow cytometry. Antigen-specific T-cell responses were evaluated seven days post-injection by collecting lymph nodes and spleen. We successfully produced αCD40-mSAs, confirmed by increased molecular weight on the light chain expressing monovalent streptavidin. Binding assays demonstrated high-affinity interactions with mouse CD40 and effective biotin binding by the mSA moiety. In vivo targeting studies using fluorescently labeled OVA peptides revealed that αCD40-mSAs significantly enhanced peptide uptake in lymph nodes, particularly by cDC1 cells and macrophages. There was a notable increase in antigen-specific T cells, with an increase of OVA-specific CD8+ T cells and increased production of cytokines IL-2 and IFN-γ upon restimulation when OVA peptides were loaded onto αCD40-mSAs. In conclusion, αCD40-mSAs represent an effective delivery platform for personalized cancer vaccines by targeting DCs and improving neoantigen peptide uptake, offering a promising strategy to boost vaccine efficacy in cancer immunotherapy. Citation Format: Dahee Jung, Xiaoying Cai, Wonkyung Oh, Seung-Oe Lim, Steve Lee. Engineered anti-CD40 agonist antibody as a novel cancer neoantigen vaccine carrier [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 6085.
Abstract 5268: Impede cancer brain metastasis by enhancing innate immunity with CCL2 targeting
Authors: Yimin Duan, Lin Zhang, Yutao Qi, Xiangliang Yuan, Dihua Yu
Journal: Cancer Research (2025)

Abstract Among the more than 300, 000 newly diagnosed breast cancer patients every year, 5∼20% of them will develop symptomatic brain metastasis (BrM) with a lower than 20% of 1-year survival rate. Our group previously reported that brain tumor microenvironment (TME)-mediated PTEN downregulation in BrM tumor cells leads to increased secretion of the CCL2 chemokine, which enhances the infiltration of CCR2+ bone marrow derived myeloid cells to promote brain metastasis outgrowth. Here, we further assessed whether targeting CCL2 can effectively inhibit BrM progression. Indeed, targeting CCL2 through either knocking-down CCL2 or with Ccl2-blocking antibody exhibited significant inhibition of BrM growth. Mass cytometry analysis of the brain TME demonstrated dramatically decreased immune suppressive myeloid populations in the CCL2-targeted group, which is consistent with our previous findings. Remarkably, natural killer (NK) and CD8+ T cells were dramatically increased in the TME of CCL2-knockdown BrMs. To test the contribution of the increased NK cells and/or CD8+ T cells on BrM inhibition by CCL2-targeting, we specifically depleted NK cells or CD8+ T cells with anti-NK1.1 or anti-CD8 antibody. Our data showed that depleting NK cells, but not CD8+ T cells, blocked BrM inhibition effect of CCL2-targeting, indicating that the increased infiltration of NK cells significantly contributed to the BrM inhibition under CCL2 knockdown. These findings led us to postulate that CCL2 inhibits NK cell infiltration into BrM TME to facilitate BrM growth. Our in vitro NK cell migration assay with high- versus low-CCL2 tumor cells showed that high CCL2 level inhibited NK cell migration. In summary, our data indicate the potential of CCL2 targeting for controlling breast cancer BrM progression and highlight the pivotal role of NK cell-mediated innate immunity in combating BrM. Citation Format: Yimin Duan, Lin Zhang, Yutao Qi, Xiangliang Yuan, Dihua Yu. Impede cancer brain metastasis by enhancing innate immunity with CCL2 targeting [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 5268.
Abstract 1993: A translational circulating tumor cell drug sensitivity screening platform for integrated drug development and precision medicine: Results from Antrodia cinnamomea profiling
Authors: Chia-Liang Yen, Pei Yu Chen, Shih Pei Wu
Journal: Cancer Research (2025)

Abstract Reliable preclinical drug sensitivity screening platforms are crucial for advancing precision medicine and drug development. We have established a circulating tumor cell (CTC) drug sensitivity screening platform that enables comprehensive applications, including treatment response prediction and molecular profiling. To demonstrate the platform's utility, we evaluated multiple compounds including Antrodia cinnamomea (AC) and standard chemotherapy across various cancer types. For the AC study, CTCs were isolated from patients (n=9) with brain tumors (n=3), osteosarcoma (n=2), renal cell carcinoma (n=1), small cell lung cancer (n=1), breast cancer (n=1), and colon adenocarcinoma (n=1). CTCs were expanded using the E.V.A. Select platform with biomimetic 3D surface structure. Cells were treated with AC (0-125 μg/mL) and responses were compared with platinum-based chemotherapy (cisplatin/carboplatin). Cell viability was assessed using CellTiter-Glo® luminescent assay after 72 hours. Our platform has also demonstrated capability for next-generation sequencing in separate drug discovery cohorts. Data analysis was assisted by artificial intelligence tools (Claude, Anthropic). AC demonstrated consistent dose-dependent cytotoxicity, with survival rates at 125 μg/mL ranging from 5.7-13.8% across cancer types. Compared to platinum drugs (survival rates 22-67%), AC showed stronger or comparable efficacy. Brain tumor samples showed particular sensitivity to AC (125 μg/mL: 5.7-13.8% survival vs. cisplatin: 66.5% survival). Osteosarcoma samples demonstrated consistent AC response (125 μg/mL: 6.1-10.0% survival vs. carboplatin: 31.4-43.5% survival). The platform has successfully supported both drug sensitivity screening and molecular profiling across multiple drug development programs. This study showcases our platform's versatility in drug sensitivity screening and comprehensive drug development applications. The E.V.A. Select platform supports both drug response profiling and molecular characterization, making it a valuable tool for drug discovery and precision medicine applications. These capabilities enable systematic evaluation of novel compounds while supporting mechanistic understanding through molecular analyses. Citation Format: Chia-Liang Yen, Pei Yu Chen, Shih Pei Wu. A translational circulating tumor cell drug sensitivity screening platform for integrated drug development and precision medicine: Results from Antrodia cinnamomea profiling [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 1993.
Abstract 1967: Plexin-B2 mediates tumor cell clustering with monocyte interactions in breast cancer metastasis
Authors: Emma Schuster, Nurmaa Dashzeveg, Fangjia Tong, Yuzhi Jia, Lamiaa El-Shennawy, Tong Zhang, Andrew Hoffmann, Kibria Golam, Youbin Zhang, Joshua Squires, Erika Ramos, Rokana Taftaf, David Scholten, Hannah Almubarak, Valery Adorno-Cruz, David Sullivan, Carolina Reduzzi, Allegra Minor, William Purev-Ochir, Rong Xu, Kalliopi Siziopikou, Leonidas Plantanias, Ami Shah, William Muller, William Gradishar, Chia-Feng Tsai, Tujin Shi, Huiping Liu
Journal: Cancer Research (2025)

Abstract The dogma of single tumor cell-mediated metastasis has been challenged by the discovery of multicellular circulating tumor cells (CTCs) clusters which are 20-50 times more likely to produce viable metastasis than single CTCs. However, the molecular mechanisms underlying CTC clusters and CTC interactions with immune cells are largely unknown. Combining integrated proteomic ranking, targeted analyses, and functional determination, we identified the transmembrane protein Plexin-B2 (PLXNB2) as one of the top hits whose expression in human primary tumors is associated with unfavorable distant metastasis-free survival. PLXNB2 expression is also enriched in CTC clusters compared to single CTCs from patients with advanced breast cancer. Loss of PLXNB2 reduces the formation of homotypic tumor cell clusters and heterotypic tumor-myeloid cell clusters in triple-negative breast cancer. Interactions between PLXNB2 and its ligand Sema4C on tumor cells mediate homotypic cluster formation, and PLXNB2 binding with Sema4A on myeloid cells (monocytes) promotes heterotypic CTC cluster formation, thereby driving lung metastasis in breast cancer. Depletion of Plxnb2 in mouse breast tumor cells also blocked CTC-myeloid cell clustering and spontaneous metastasis in immune-competent mice. Additionally, using global proteomic analysis, we identified novel downstream effectors of the PLXNB2 pathway associated with tumor cell clustering in breast cancer. Thus, PLXNB2 is a novel therapeutic target for preventing new metastasis in triple-negative breast cancer. Citation Format: Emma Schuster, Nurmaa Dashzeveg, Fangjia Tong, Yuzhi Jia, Lamiaa El-Shennawy, Tong Zhang, Andrew Hoffmann, Kibria Golam, Youbin Zhang, Joshua Squires, Erika Ramos, Rokana Taftaf, David Scholten, Hannah Almubarak, Valery Adorno-Cruz, David Sullivan, Carolina Reduzzi, Allegra Minor, William Purev-Ochir, Rong Xu, Kalliopi Siziopikou, Leonidas Plantanias, Ami Shah, William Muller, William Gradishar, Chia-Feng Tsai, Tujin Shi, Huiping Liu. Plexin-B2 mediates tumor cell clustering with monocyte interactions in breast cancer metastasis. [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 1967.
Abstract 6741: AT65474, a highly selective anti-CLDN6 ADC with a proprietary payload
Authors: Chen Zhong, Yin Wen Cheng, You Xue Wu, Xi Yun Zhang, Rui Yang Zhao, Qian Wang, Ping Du, Shao Jun Liu, Bin Zou
Journal: Cancer Research (2025)

Abstract CLDN6 is a membrane-bound oncofetal protein and a promising target for cancers such as ovarian and testicular cancer. AT65474 is an antibody drug conjugate (ADC) candidate composed of a highly selective humanized anti-CLDN6 antibody conjugated to a proprietary payload, namely TCS132, with a drug-to-antibody (DAR) ratio of 4. The antibody is engineered to incorporate AxcynCYSTM technology for site-specific conjugation which can reproducibly achieve high DAR4 ratios of greater than 97% by HIC analysis. The payload, TCS132, is derived from an FDA approved drug and when compared to the parent drug, demonstrates increased potency with broad sub-nanomolar activities across a wide range of cancer cell lines including those resistant to paclitaxel, DM1, MMAE and DXd. Additionally, TCS132 was chemically optimized for better PK properties and demonstrates a much-improved safety profile despite its increased potency over the parent drug. In vitro, AT65474 specifically binds to CLDN6 presenting tumor cells and upon internalization into lysosomes, releases the payload effectively inhibiting tumor cell proliferation. AT65474 displays a bystander killing effect that enables it to kill surrounding CLDN6-negative tumor cells, further enhancing its anti-proliferative effects. In vivo, AT65474 shows strong anti-tumor activity in CLDN6-positive CDX and PDX models at low doses and long intervals, which reflects the elevated payload levels in the tumors. Furthermore, safety assessment of AT65474 including GLP-compliant toxicology studies in Cynomolgus monkeys and SD rats reveals a good safety profile of AT65474. Taken together, the results of the nonclinical studies support the intended clinical trial, dose selection, and regimen in humans. Citation Format: Chen Zhong, Yin Wen Cheng, You Xue Wu, Xi Yun Zhang, Rui Yang Zhao, Qian Wang, Ping Du, Shao Jun Liu, Bin Zou. AT65474, a highly selective anti-CLDN6 ADC with a proprietary payload [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 6741.