tbuckley/cabot-search huggingface dataset:
Abstract 6117: Development of preclinical models for the evaluation of conventional and <i>in vivo</i> CAR-T therapies
Authors: Hongyan Sun, Xiaoliu Yang, Shiying Guo, Jianming Xu, Xiang Gao, Jun Wang
Journal: Cancer Research (2025)

Conventional CAR-T manufacturing involves ex vivo expansion and engineering of T cells either from patients (autologous) or healthy donors (allogenic), which is time- and cost-consuming. The recent advancement of in vivo gene editing using lentiviral vectors allows CAR-T generation in vivo, which is time- and cost-effective compared to the conventional approaches. To evaluate their in vivo anti-tumor efficacy and toxicity, genetically engineered mouse models which express the human-specific target represent a viable choice for preclinical testing. While immunodeficient mouse models are crucial for preclinical evaluation, their utility is often compromised by the development of graft-versus-host disease (GvHD). To overcome this limitation, GemPharmatech has developed a novel NCG-MHC-dKO mouse model, which combined severe immunodeficiency with MHC class I and II molecules knockout to minimize GvHD occurrence and extend treatment window. We assessed the efficacy of an in vivo CAR-T vector using this newly developed model. NCG-MHC-dKO mice bearing luciferase-tagged Nalm6 tumors received intraperitoneal injection of 2×107 PBMCs, followed by administration of a single dose of the lentiviral vector encoding an anti-CD19 CAR transgene. Successful in vivo gene editing was confirmed by flow cytometry analysis using antibodies specific for CAR in reconstituted human T cells. Tumor burden was monitored longitudinally using an In Vivo bioluminescence Imaging System (IVIS®), quantified as total bioluminescent flux. The in vivo CAR-T vector treatment demonstrated robust growth inhibition of Nalm6-Luc tumor in huPBMC-NCG-MHC-dKO mice, with minimal GvHD occurrence throughout the course of the study, while mock-treated groups did not show any obvious tumor growth inhibition, confirming the specificity of the CAR-T vector. These findings established the NCG-MHC-dKO mouse model with PBMC engraftment as a suitable platform for preclinical evaluation of both conventional and in vivo CAR-T therapeutic strategies. Citation Format: Hongyan Sun, Xiaoliu Yang, Shiying Guo, Jianming Xu, Xiang Gao, Jun Wang. Development of preclinical models for the evaluation of conventional and in vivo CAR-T therapies [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 6117.
Abstract 54: Comparative preclinical antitumor assessment of 5FU versus anti-PD1 using in vivo imaging system in MC38 orthotopic tumor model
Authors: Balaji Ramachandran, Ravindra Ghodke, Satheeshkumar Rajendiran, Bhanupranav Skanda, Krishnappa Haladasappa, Sachin Joshi
Journal: Cancer Research (2025)

Abstract Immunotherapy has evolved as potential and practical therapeutic options for primary and metastatic tumors. Orthotopically implanted tumor models are clinically relevant and however growth monitoring of orthotopic tumor &amp; assessing efficacy outcomes poses a practical challenge. Optical imaging by In Vivo Imaging System (IVIS) is a valuable method to monitor the real time progression of in vivo tumor growth without implying the need for interim termination during the study. In the present study, we have evaluated the preclinical efficacy of 5- Fluorouracil in combination with mouse anti-PD1 antibody in orthotopic MC38 model in immunocompetent mice. Subcutaneous tumor was generated in donor mice by inoculation of MC38 luciferase reporter cell line. Tumor fragments (∼30mg) harvested from the donor mice were orthotopically implanted on the subserosal layer of cecum of C57BL/6 mice. Tumor growth was monitored twice weekly by IVIS optical imaging system. Mice were randomized based on total flux signal intensity (1-3 X 106 photons/second). Standalone &amp; combination treatment was initiated with 5-FU; 25 mg/kg, i.p; Q2D and anti-PD-1 at 5 mg/kg, ip; Q4D x 4 doses. Total flux (photons/second), changes in body weight, clinicals signs, mortality were monitored twice weekly up to 2 weeks. At the end of the study, ex vivo bioluminescence signal intensity and tumor weights were recorded. In the current MC38 orthotopic tumor model, standalone treatment of anti-PD-1 and 5-FU resulted in moderate tumor regression. However, combination of 5-FU with anti-PD1 resulted in improved efficacy when compared with individual treatments which was evident from the reduction in signal intensity. In conclusion, evaluating efficacy of combinations treatment in preclinical orthotopic tumor models using IVIS imaging will be helpful tool for an accurate, non-invasive longitudinal monitoring of tumor growth over extended duration. Citation Format: Balaji Ramachandran, Ravindra Ghodke, Satheeshkumar Rajendiran, Bhanupranav Skanda, Krishnappa Haladasappa, Sachin Joshi. Comparative preclinical antitumor assessment of 5FU versus anti-PD1 using in vivo imaging system in MC38 orthotopic tumor model [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 54.
Abstract 5770: Single-cell Raman-based omics of the melanoma tumor-immune microenvironment for precision therapy
Authors: Kai Chang, Mamatha Serasanambati, Baba Ogunlade, Ariel Stiber, Fareeha Safir, Hamish Carr Delgado, Amanda Kirane, Jennifer Dionne
Journal: Cancer Research (2025)

Abstract Immunotherapy and targeted therapy have altered the standard of care for cancer patients, improving survival rates and cancer control, even in intransigent metastasis. Yet, only 20-40% of patients respond to immunotherapy, and up to 50% experience severe adverse events, limiting therapy application. Notably, cellular heterogeneity and diversity in the makeup of the tumor immune microenvironment (TiME) present extraordinary challenges in finding predictive biomarkers correlating to therapeutic response. Existing profiling methods, even with highly resolved, cutting-edge transcriptomic and proteomic mapping methods remain costly, time-intensive, and do not faithfully capture structural or post-translational modifications actively impacting tumor behavior. Here, we present a high-fidelity, single-cell omics approach based on Raman spectroscopy and machine learning to provide rapid, cellular profiling that enables non-destructive therapeutic response characterization. Using Raman, we first demonstrate single-cell differentiation and functional state phenotyping of various melanoma and immune cells found in the TiME. Our ML models yield a classification accuracy of &amp;gt;94% across all cell types and parent and derivative cancer lines. We then extend our characterization to track temporal changes across multicellular systems; by investigating cell growth in normal and apoptotic-inducing environments, we show how melanoma-immune cell interactions preserve certain spectral features while introducing new features via cell fusioning under selective pressures. By stimulating cells with small molecule therapeutics serving as growth and inhibiting factors, we demonstrate the potential to monitor melanoma cell plasticity and macrophage polarization changes. Finally, we illustrate the potency of Raman phenotyping by examining the collective drug response in clinically relevant patient melanoma samples and extract pertinent biomarkers associated with small molecule and immunotherapy treatment outcomes. In combination with neural networks, our approach correctly predicts therapy response with &amp;gt;75% accuracy for unseen melanoma patient samples, demonstrating Raman as a powerful rapid, label-free omics approach with groundbreaking potential to advance clinical biomarker efforts and impact the precision treatment decisions of cancer patients. Citation Format: Kai Chang, Mamatha Serasanambati, Baba Ogunlade, Ariel Stiber, Fareeha Safir, Hamish Carr Delgado. Single-cell Raman-based omics of the melanoma tumor-immune microenvironment for precision therapy [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 5770.
Abstract 5784: An image based assay platform for drug screening with a 3D bioprinted vascularized lung cancer model
Authors: Fahimeh Shahabipour, Yuchi Yuchi Chen, Yen-Ting Tung, Marc Ferrer, Min Jae Song
Journal: Cancer Research (2025)

Abstract 3D tissue models that mimic the physiology of human tissues and organs are being developed in multi-well plate format as predictive assays for drug screening. 3D bioprinting enables the fabrication of tissues with precision and reproducibility in a 96-well plate for medium throughput drug screening. We have established robust protocols for the 3D bioprinting vascularized lung tissue models using human primary pulmonary endothelial cells constitutively expressing green fluorescent protein (GFP), pericytes, and fibroblasts mixed with a fibrin-based hydrogel. We create a vascularized lung tissue model in a ring-shaped structure that facilitates image-based quantification of vasculogenesis and angiogenesis. This bioprinted vascularized lung tissue model was used as a tumor microenvironment to grow lung cancer cells. We incorporated three immortalized lung cancer cell lines, A549, H1975, and H460, constitutively expressing red fluorescent protein (RFP) into the 3D bioprinted vascularized lung tissues. Cancer cells were added as single cells embedded in the hydrogel (1K cancer cells/well) covering the bioprinted vasculature. Fluorescence microscopy was used to quantify the growth and morphology of the cancer cells by measuring total red fluorescence intensity surface roundness and compactness of red fluorescence objects, as well as angiogenesis from the green fluorescence intensity. After 21 days of culture, the three cancer cell lines showed distinct growth morphology and migration patterns. We characterized tumor localization according to the three regions of interest: angiogenesis outwards or inwards and tumor growth inside or outside the bioprinted vasculature area. A549 and H1975 showed a strong tendency to migrate towards the bioprinted vascularized structure, growing as low compact structures. The H460 cell line formed small compact spheroid structures and did not prefer the vasculature area. We also compared cancer cell growth and morphology with and without vascular components to assess any effects of the vasculature on tumor growth. We observed that this study helps demonstrate the usefulness of the bioprinted vascularized lung tissue cancer model as an assay platform for screening for anti-cancer drugs in an assay that includes the tumor microenvironment. Keywords: 3D bioprinted, 3D cancer-vascularized lung tissue model, drug Screening, Citation Format: Fahimeh Shahabipour, Yuchi Yuchi Chen, Yen-Ting Tung, Marc Ferrer, Min Jae Song. An image based assay platform for drug screening with a 3D bioprinted vascularized lung cancer model [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 5784.
Abstract 5397: Role of pyruvate carboxylase in cancer-associated fibroblasts under tumor nutrient stress
Authors: Michał Nizio, Marta Storl-Desmond, Kevin Muñoz Forti, Julien Guillard, Shan Cao, Kristof Turan, Alexander Muir, Simon Schwörer
Journal: Cancer Research (2025)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and hard-to-treat cancer types. PDAC is characterized by desmoplastic stroma enriched with extracellular matrix (ECM), immune cells and cancer-associated fibroblasts (CAFs). CAFs modulate PDAC progression by producing ECM and signaling molecules that influence cancer and immune cell function. Previous efforts to target CAFs’ role in PDAC were unsuccessful but have instead revealed substantial heterogeneity within the CAF population. Two main subtypes of CAFs are tumor-restraining myofibroblastic CAFs (myCAFs) and tumor-promoting inflammatory CAFs (iCAFs). To effectively target CAFs in PDAC, there is a need to find CAF-state-specific vulnerabilities and mechanisms regulating CAF state. We discovered that myCAFs are excluded from hypoxic and nutrient-stressed regions of PDAC, and iCAFs are selectively enriched in those regions. Pyruvate carboxylase (PC) is an enzyme that allows cells to utilize pyruvate as an anaplerotic substrate. Our previous work showed that PC is important for CAFs under nutrient-stressed conditions. Here, we hypothesize that PC is required to promote the iCAF state and support their growth in the nutrient-stressed environments they occupy. To address this hypothesis, we acclimated pancreatic stellate cells (PSCs), CAF precursors in PDAC, to physiological media resembling the concentration of nutrients in human plasma (HPLM - human plasma-like medium) or PDAC (TIFM - tumor interstitial fluid medium). We used CRISPR/Cas9 to delete PC, allowing us to investigate the role of PC in PSCs under physiological conditions. We observed that PC expression is higher in cells cultured in TIFM than in HPLM or conventional RPMI. We confirmed higher PC activity in TIFM compared to HPLM or RPMI cultured cells using stable isotope tracing. These findings indicate that PC expression and activity are regulated by the nutrient conditions present in PDAC and suggest that PC might be selectively important in CAFs under tumor nutrient stress. A better understanding of PC’s role in CAFs residing in nutrient-stressed niches in PDAC may lead to the discovery of a novel way of targeting tumor-promoting iCAFs. Citation Format: Michał Nizio, Marta Storl-Desmond, Kevin Muñoz Forti, Julien Guillard, Shan Cao, Kristof Turan, Alexander Muir, Simon Schwörer. Role of pyruvate carboxylase in cancer-associated fibroblasts under tumor nutrient stress [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 5397.
Abstract 7239: Investigating the role of topoisomerase IIB in the regulation of antigen presentation pathway in high-grade serous ovarian cancer
Authors: Shraddha G. Gupta, Sangeeta Kumari, Adam Karami, Aisha Jamil, Sergey Karakashev
Journal: Cancer Research (2025)

Abstract Epithelial ovarian cancer (EOC) is the deadliest gynecologic malignancy and accounts for 90% of ovarian tumors. High grade serous ovarian cancer (HGSOC), an aggressive subtype of EOC, develops rapidly and is correlated with poor prognosis. Importantly, HGSOC accounts for 70-80% of deaths related to ovarian cancer. Immunotherapies that have revolutionized the field of cancer therapy demonstrate limited therapeutic efficacy in HGSOC. HGSOC tumors are characterized by low immune cell infiltration and reduced anti-tumor immune response. Hence, it is crucial to develop new therapeutic strategies that improve anti-tumor immune response in HGSOC. Epigenetic suppression of antigen processing and presentation pathway (APP) is one of the major mechanisms adopted by cancer cells to escape T-cell cytotoxicity. APP entails binding of the cytotoxic CD8+ T cells to neoantigen presented by Major Histocompatibility Complex Class I (MHC class I) on the membrane of cancer cells. Neoantigen recognition by CD8+ T cells lead to activation of CD8+T cells and subsequent killing of the antigen-presenting cells (APC). Previous studies have demonstrated that defects in the expressions and functions of APP components correlate with reduced T-cell infiltration, metastasis, and poor overall survival. Our bioinformatics analysis of publicly available ovarian cancer patient dataset from The Cancer Genome Atlas (TCGA) and ovarian cancer cell line database (Depmap) revealed DNA topoisomerase 2-beta (TOP2B) as a potential negative regulator of APP. TOP2B is a topoisomerase that regulates the transcription of its target genes by altering the topological state of DNA. Recently, a small molecule inhibitor, CX-5461, was discovered to specifically target TOP2B. It has also completed Phase I clinical trials for solid tumor and hematological malignancies demonstrating its safety and efficacy in human patients. Understanding the role of TOP2B in cancer progression may lead to the development of a novel therapeutic strategy to improve overall survival of HGSOC patients. Citation Format: Shraddha G. Gupta, Sangeeta Kumari, Adam Karami, Aisha Jamil, Sergey Karakashev. Investigating the role of topoisomerase IIB in the regulation of antigen presentation pathway in high-grade serous ovarian 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 7239.
Abstract 1635: Targeting ferroptosis in CCDC88A-overexpressing metastatic triple-negative breast cancer
Authors: Wei-Ling Tu, Mu-En Wang, Ji-Hoon Kim, Alyssa Bawcom, Yi Lu, Ming Chen
Journal: Cancer Research (2025)

Abstract Triple-negative breast cancer (TNBC) is a form of breast cancer that does not express estrogen receptor (ER), progesterone receptors (PR) or human epidermal growth factor receptor 2 (HER2). It accounts for 15-20% of all breast carcinomas and preferentially affects women who are African American, younger than age 40, or have a BRCA1 mutation. The TNBC subtype is highly aggressive and heterogeneous and has a poor prognosis relative to other breast cancer subtypes due to a lack of highly recurrent and actionable biomarkers that can be used to direct therapy. Although standard chemotherapies show a high initial response rate in TNBC, tumor relapses and metastasis often occur rapidly. Moreover, for patients who have recurrent disease or progressive disease during chemotherapy, treatment options are limited. Therefore, there is an unmet need to identify effective therapies targeting TNBC. By analyzing public human datasets, we found that CCDC88A (also known as Girdin or GIV), a putative oncogene, is highly expressed in TNBC compared to other breast cancer subtypes. CCDC88A has been found to be involved in key cancer development events such as tumor angiogenesis, invasion, wound healing, and metastasis. Interestingly, we found that, although the high expression of CCDC88A conferred the ability of lung metastasis, it increased the susceptibility of TNBC to ferroptosis, a type of cell death induced by iron-dependent lipid peroxidation. Mechanistically, CCDC88A sensitized TNBC cells to ferroptosis by limiting intracellular glutathione (GSH) levels. shRNA-mediated CCDC88A knockdown in TNBC cells significantly increased GSH levels and in turn blunted cellular sensitivity to ferroptosis. On the other hand, inhibition of GSH synthesis with a glutamate-cysteine ligase (GCL) inhibitor, BSO, restored the ferroptosis sensitivity in CCDC88A knocked-down TNBC cells. Thus, our findings uncover CCDC88A as a novel ferroptosis regulator and also suggest that ferroptosis is a therapeutically tractable target for metastatic TNBC that overexpresses CCDC88A. Citation Format: Wei-Ling Tu, Mu-En Wang, Ji-Hoon Kim, Alyssa Bawcom, Yi Lu, Ming Chen. Targeting ferroptosis in CCDC88A-overexpressing metastatic triple-negative breast 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 1635.
Abstract 4588: Cell states and resistance in colorectal cancer: What can we learn from patient-derived organoids?
Authors: Maxim Norkin, Pablo Hernandez Lopez, Cinzia Esposito, George Ramzy, Mireia Andreu Carbo, Paloma Ordóñez-Morán, Patrycja Nowak-Sliwinska, Salvatore Piscuoglio, Krisztian Homicsko, Joerg Huelsken
Journal: Cancer Research (2025)

Colorectal cancer (CRC) is among the three most commonly diagnosed cancers and one of the major causes of cancer-related morbidity and mortality. Despite the discovery of several predictive biomarkers, the 5-year survival rate for metastatic CRC is 15%. A hallmark of CRC is inter- and intra-patient heterogeneity. Moreover, chemo-radiation and targeted therapies often result in producing resistant clonal populations that are unresponsive to the ongoing treatment. Revealing a comprehensive landscape of primary and metastatic CRC cell states and their evolution during chemotherapy treatment provides the potential for tackling this problem. Patient-derived organoids are a valuable research tool to study the biology of the disease as well as for drug screening in personalized medicine. To that end, we have collected a biobank of 90 PDOs from primary and metastatic CRC patients, as well as autologous cancer-associated fibroblasts (CAFs) and tumor infiltrating lymphocytes (TILs). We have performed whole-exome sequencing (WES), scRNA-seq and bulk RNA-seq of original tumors and PDOs, with and without chemotherapy treatment. We have discovered specific and common transcriptional cell states within PDOs and tumors, as well as the multiple responses to treatment confirming high heterogeneity of CRC. Combination of these results with clinical data can predict new biomarkers. Citation Format: Maxim Norkin, Pablo Hernandez Lopez, Cinzia Esposito, George Ramzy, Mireia Andreu Carbo, Paloma Ordóñez-Morán, Patrycja Nowak-Sliwinska, Salvatore Piscuoglio, Krisztian Homicsko, Joerg Huelsken. Cell states and resistance in colorectal cancer: What can we learn from patient-derived organoids [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 4588.