tbuckley/cabot-search huggingface dataset:
Abstract 3511: A T cell engager (TCE), HB134, targeting LILRB4 and CD3, exhibits potent anti-tumor activity with a favorable safety profile for monocytic AML
Authors: Juan Liu, Fangfang Ren, Chunmei Liu, Jing Shao, Fang Yang, Jianhe Chen, Bin Ye, Jianhua Sui
Journal: Cancer Research (2025)

Abstract Background: Acute myeloid leukemia (AML), is a heterogeneous and highly aggressive malignancy, characterized by poor prognosis and limited treatment options. Monocytic AML, including M4 and M5 subtypes, presents a significant clinical challenge due to its dismal prognosis and high relapse rates post-transplant. The leukocyte immunoglobulin-like receptor B4 (LILRB4) is overexpressed in monocytic AML but is absent in normal hematopoietic stem cells, highlighting its potential as a therapeutic target. Here, we report the development of a novel TCE targeting LILRB4 and CD3, HB134, for the treatment of monocytic AML. Methods: The HB134 TCE was generated by fusing an anti-LILRB4 nanobody and an anti-CD3 Fab to a human IgG1 with a silent Fc region. Surface plasmon resonance, enzyme-linked immunosorbent assay, and flow cytometry were used to measure HB134’s binding activities to LILRB4 and CD3. Luciferase-based cellular reporter assays and a primary T cell-dependent cellular cytotoxicity (TDCC) assay using peripheral blood mononuclear cells (PBMCs) were employed to assess HB134’s T cell activation activity. Additionally, in vivo anti-tumor efficacy and pharmacokinetic (PK) profile were evaluated in mouse models. Results: HB134 exhibited sub nanomolar high binding affinity for human LILRB4 and low binding affinity to human CD3. In the cellular luciferase reporter assays, in the presence of LILRB4-positive monocytic AML cells (THP-1 or MOLM-13 cell line), HB134 induced robust T cell activation; in contrast, no T cell activation was observed in the presence of LILRB4-negative cells, indicting HB134 can specifically induce T cell activation in a LILRB4-engagement-dependent manner. In the TDCC assays using PBMCs, HB134 induced potent cytotoxicity against LILRB4-positive THP-1 and MOLM-13 cells with limited induction of cytokine release syndrome-related proinflammatory cytokines, including IL-6 and TNF-α. In an immunodeficient mouse model engrafted with human PBMCs and LILRB4-positive THP-1-luciferase cells, HB134 showed potent anti-tumor efficacy. Additionally, HB134 demonstrated a favorable PK profile in BALB/c mice. Conclusions: HB134, a TCE designed to engage T cells via CD3 and specifically target LILRB4, exhibits potent anti-tumor activity and favorable PK and safety profiles, positioning HB134 as a promising therapeutic candidate for treating LILRB4-positive monocytic AML. Citation Format: Juan Liu, Fangfang Ren, Chunmei Liu, Jing Shao, Fang Yang, Jianhe Chen, Bin Ye, Jianhua Sui. A T cell engager (TCE), HB134, targeting LILRB4 and CD3, exhibits potent anti-tumor activity with a favorable safety profile for monocytic AML [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 3511.
Abstract 3676: Ultrasensitive protein detection using proximity initiated nucleic acid target amplification with digital biosensing
Authors: Skye Shepherd, Weinan Liu, Brian T. Cunningham
Journal: Cancer Research (2025)

Abstract Proteins are vital biomarkers and provide a real-time dynamic look into cancer progression and disease states. Point-of-care simple diagnostics for rapid, ultrasensitive testing is necessary to study longitudinal changes of protein biomarkers for treatment monitoring, prognosis, or early detection. Proximity assays are a solution-based protein assay using antibody pairs that can achieve high sensitivity, specificity, and be used for high-throughput or multiplexing applications. However, standard proximity assays require complicated design, enzymatic amplification such as polymerase chain reaction (PCR), and thermocycling with expensive laboratory equipment and specialized laboratories. This limits the use for longitudinal monitoring or liquid biopsies. We demonstrate here the Proximity Initiated Nucleic Acid Target Amplification (PINATA) assay, a novel proximity immunoassay for protein detection that can be performed completely at room temperature in a single step using a small, portable, point-of-care benchtop detection instrument. The PINATA assay implements linear amplification using toehold-mediated strand displacement reactions of antibody-oligonucleotide conjugates along with digital detection of individual gold nanoparticle tags for ultrasensitive, rapid protein quantification in the femtomolar range, allowing detection in less than two hours for sub picogram per milliliter concentrations of human interleukin 6, a cytokine biomarker of inflammation that has been linked to certain cancers. These results showcase the promise of entropy-driven strand displacement proximity assays for fast and ultrasensitive point-of-care applications and disease diagnostics. Citation Format: Skye Shepherd, Weinan Liu, Brian T. Cunningham. Ultrasensitive protein detection using proximity initiated nucleic acid target amplification with digital biosensing [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 3676.
Abstract 132: Collagen I triggers a GCN2-mediated integrated stress response to promote cancer cell survival
Authors: Mark Ellie De Boton Alonzo, Ethan Jadon Subel, Hongbo (Beth) Gao, Stephen QR Wong, Yung Hsing Huang, David Chang, Grace Wong, Mustafa Karabicici, Sung Yun Jung, Fotis Nikolos, Keith Syson Chan
Journal: Cancer Research (2025)

Abstract Bladder cancer (BLCA) is the 6th most commonly diagnosed cancer in the US. Despite recent advances, BLCA has a high recurrence rate. Increased deposition of the extracellular matrix Collagen I (Col I) is a hallmark of cancer progression and correlates with poor patient survival in BLCA. Recent studies have showcased the dynamic nature of Col I, which signals key pro-tumoral processes like immune evasion and metastasis. Interestingly, Col I limits nutrient access and oxygen to adjacent tumors in the tumor microenvironment. Cancer cells adapt to disadvantageous conditions by activating pathways such as the integrated stress response (ISR) to downregulate mRNA translation to promote survival. High activity of ISR and its related proteins in cancer cells also increase chemoresistance, dormancy and metastasis. How Col I plays a role in activating pro-survival ISR in BLCA remains to be investigated. In this study, we describe the direct role of Col I in exploiting ISR in BLCA, increasing its tumorigenic capacity. We uncover that Col I rapidly downregulates global mRNA translation by inducing ISR, while promoting spheroid size in vitro and tumor growth in vivo. Mechanistically, Col I induces intracellular amino acid deprivation thereby activating GCN2, an important amino acid sensor and a key kinase mediating ISR. Inhibition of GCN2 and subsequent ISR activity is an effective therapeutic target in multiple cancer types. Here, we show pharmaceutical inhibition of GCN2 disrupts ISR, rescuing translation while decreasing Col I-induced spheroid and tumor growth. Clinically, analysis of the TCGA BLCA dataset reveal both high expression of ISR-associated genes and a high GCN2-mediated signaling pathway score correlate with poor overall survival. GCN2 and ISR pathway scores also correlate with high Col I expression, further indicating their involvement in promoting BLCA tumorigenesis. These findings unravel a novel mechanism by which Col I utilizes the ISR pathway to promote BLCA tumorigenesis and provides a potential therapeutic targets for BLCA patients in the future. Citation Format: Mark Ellie De Boton Alonzo, Ethan Jadon Subel, Hongbo (Beth) Gao, Stephen QR Wong, Yung Hsing Huang, 2David Chang, 2Grace Wong, 2Mustafa Karabicici, 1Sung Yun Jung, 3Fotis Nikolos, 2Keith Syson Chan2. Collagen I triggers a GCN2-mediated integrated stress response to promote cancer cell survival [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 132.
Abstract 3175: Exploring the potential of CEA-CAR-NK cells in colorectal cancer
Authors: Alice D'Andrea, Marco Cortese, Enzo Medico
Journal: Cancer Research (2025)

Chimeric Antigen Receptor (CAR) therapy targeting carcinoembryonic antigen (CEA/CEACAM5) is a promising strategy for colorectal cancer (CRC). CAR-T cells, however, carry significant side effects, and the fact that CEA is also expressed at low levels in normal tissues makes CAR-NK cells a safer alternative, offering reduced toxicity while maintaining effective anti-tumor activity. Despite this potential, CAR-NK systems targeting CEA remain underexplored. In this study, we generated and evaluated clones of the NK-92 cell line expressing two CAR constructs with distinct affinity for CEA: BW431/26 (moderate affinity) and hMN-14 (high affinity). The BW431/26-based CAR, with its lower affinity, may offer a safer profile by reducing potential on-target, off-tumor effects. On the other hand, the hMN-14-based CAR demonstrated superior cytotoxicity in in vitro studies due to its higher affinity. Sorted populations and clones of CAR-NK cells transduced with these constructs were evaluated for killing activity both in vitro and in vivo. In vitro, the high affinity hMN-14 CAR exhibited enhanced killing capacity compared to the BW431/26 CAR. However, in vivo experiments on CRC xenografts in NOD/Scid mice showed comparable tumor growth inhibition between the two constructs. These findings suggest that higher scFv affinity does not necessarily translate to improved in vivo efficacy of CEA-CAR-NK cells, emphasizing the multiplicity of factors influencing their activity—such as persistence and activation—and highlighting the need for further modifications to optimize their functionality. Citation Format: Alice D'Andrea, Marco Cortese, Enzo Medico. Exploring the potential of CEA-CAR-NK cells in 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 3175.
Abstract 856: Exploiting the molecular mimicry for preventive/therapeutic cancer vaccine development
Authors: Maria Tagliamonte, Beatrice Cavalluzzo, Angela Mauriello, Concetta Ragone, Biancamaria Cembrola, Simona Mangano, Luigi Buonaguro
Journal: Cancer Research (2025)

Abstract Shared tumor antigens are needed for developing off-the-shelf preventive/therapeutic cancer vaccines. To this aim, shared mutated neoantigens (TSAs) cannot be exploited for highly prevalent tumors in the majority of worldwide cancer patients. Therefore, TAAs must be used, which may suffer from the potential immunological tolerance. Analogue peptides with improved antigenicity and immunogenicity, able to elicit a cross-reactive T cell response are needed. To this aim, non-self-antigens derived from microorganisms (MoAs) may be of great benefit. We will describe several examples of MoAs sharing sequence homology with TAAs (“molecular mimicry”), able to elicit a cross-reacting CD8+ T cell response. In particular, the homology to cancer testis TAA (e.g. MAGE-A1) allows to develop cancer vaccines useful for several tumor types, “one-vaccine-for-many-tumors”. In conclusion, non-self MoAs should be selected and included in preventive/therapeutic cancer vaccines with a more potent anti-tumor efficacy compared to those based on TAAs. This would allow the development of ready to be used “off-the-shelf” cancer vaccines for the global population of patients affected by one or more cancer types (Tagliamonte M, et al., Molecular mimicry and cancer vaccine development. Mol Cancer. 2023 Apr 26;22(1):75. doi: 10.1186/s12943-023-01776-0). Citation Format: Maria Tagliamonte, Beatrice Cavalluzzo, Angela Mauriello, Concetta Ragone, Biancamaria Cembrola, Simona Mangano, Luigi Buonaguro. Exploiting the molecular mimicry for preventive/therapeutic cancer vaccine development [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 856.
Abstract 87: Targeting POU5F1-expressing circulating tumor cells to prevent metastasis and recurrence in colorectal cancer
Authors: Shiki Fujino, Aya Ito, Rie Hayashi, Masayoshi Yasui, Masayuki Ohue, Norikatsu Miyoshi
Journal: Cancer Research (2025)

Abstract Background: Recurrence and metastasis following curative treatment remain significant challenges in colorectal cancer (CRC). Circulating tumor cells (CTCs) are pivotal in the dissemination of cancer, leading to distant metastases and eventual recurrence. Despite their importance, the cellular lineages driving these processes in CRC remain poorly defined. POU5F1, a transcription factor associated with stemness, is highly expressed in recurrent CRC tumors and is linked to poor prognosis and a high incidence of liver metastasis. Methods: We developed a patient-derived cancer cell model, termed isolated tumor-derived cancer cells, cultured as two-dimensional organoids (2DOs). These 2DOs retain tumor heterogeneity and tumor microenvironment interactions, providing a robust platform for investigating treatment-resistant lineages. Using EGFP-reporter 2DOs, POU5F1-expressing cells were isolated and characterized through drug sensitivity assays, single-cell RNA sequencing, immunocytochemistry, and epigenetic analyses. Therapeutic studies were conducted to evaluate the efficacy of targeting key pathways. Results: POU5F1-expressing cells were highly enriched in blood samples from relapsed CRC patients as CTCs. These cells exhibited cancer stem cell properties, including self-renewal and differentiation, and demonstrated a high capacity for liver metastasis in vivo. Single-cell RNA sequencing revealed that POU5F1-positive cells generate heterogeneous populations enriched in the Wnt signaling pathway. Immunocytochemistry confirmed the co-expression of POU5F1 and CTLA4, with epigenetic analysis showing demethylation at transcriptional start sites of both genes, implicating epigenetic regulation in their aggressiveness. The Wnt/β-catenin pathway inhibitor XAV939 effectively suppressed adhesion and survival of POU5F1-positive cells in vitro. Remarkably, early administration of XAV939 completely inhibited liver metastasis induced by these cells in vivo. Conclusions: POU5F1-expressing cells are critical drivers of CRC metastasis and recurrence, exhibiting stem-like properties and treatment resistance. Their enrichment in Wnt signaling and CTLA4 expression identifies actionable therapeutic targets. Our findings highlight the potential of Wnt/β-catenin inhibitors like XAV939 to prevent CRC metastasis and recurrence, paving the way for improved therapeutic strategies in high-risk patients. Citation Format: Shiki Fujino, Aya Ito, Rie Hayashi, Masayoshi Yasui, Masayuki Ohue, Norikatsu Miyoshi. Targeting POU5F1-expressing circulating tumor cells to prevent metastasis and recurrence in 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 87.
Abstract 3160: Silicon membrane technology enables novel live-cell assays for screening impermeable compounds prior to medchem optimization
Authors: Zhihui Song, Sophia Hirsch, Andrew Laroque, Jacquelyn Hanson, Alec Barclay, Armon Sharei, Darby Kreienberg, Eleni Rogers, Monique Richards, Crystal Tsui
Journal: Cancer Research (2025)

Abstract Cell permeability poses a significant challenge to understanding target biology and exploring structure/function interactions of potential drug candidates. As a result, many experiments are performed in biochemical or lysate-based systems, which often fail to replicate the conditions of a live cell, leading to expensive and time-consuming downstream failures. Portal Biotechnologies has created an innovative intracellular delivery platform that leverages silicon membrane-based mechanoporation technology to directly deliver otherwise non-permeable cargos, such as small molecules, peptides, PROTACs, DELs, macrocycles, and probes, into the cytosol. Our research shows that mechanoporation causes minimal disruption to cellular function compared to other techniques like electroporation, which tend to impose stricter cargo limitations and inflict more cellular damage. This platform has also shown early success in delivering probe molecules for innovative intracellular assays, including LgBiT/HiBiT systems for protein degradation studies. Furthermore, we have demonstrated efficient co-delivery of diverse cargos like oligonucleotides, antibodies, and nucleic acids, achieving delivery rates exceeding 80% while maintaining cell viability above 80%.The platform has been validated across a variety of cell types, including widely used cancer cell lines and primary cells such as human immune cells and stem cells. The straightforward mechanical delivery approach enables scalability and seamless integration with liquid-handling systems for high-throughput applications. This capability allows for the automated screening of molecules previously unsuitable for live-cell assays, thereby enhancing the efficiency of drug discovery at multiple stages. By enabling live-cell assays, the Portal platform aims to offer novel biological insights, reduce target-related risks, and lower the likelihood of failures during lead optimization. Citation Format: Zhihui Song, Sophia Hirsch, Andrew Laroque, Jacquelyn Hanson, Alec Barclay, Armon Sharei, Darby Kreienberg, Eleni Rogers, Monique Richards, Crystal Tsui. Silicon membrane technology enables novel live-cell assays for screening impermeable compounds prior to medchem optimization. [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 3160.
Abstract 3674: Predicting chromatin organization from cell-free DNA fragmentation patterns
Authors: Ravi Bandaru, Zhihan Zhou, Hailu Fu, Weimin Wu, Haizi Zheng, Rashmi S. Hegde, Li Wang, Han Liu, Yaping Liu
Journal: Cancer Research (2025)

Abstract Epigenetic regulation, including the three-dimensional (3D) architecture of the genome, plays a critical role in gene expression and cellular function. Aberrations in chromatin organization are implicated in various diseases, particularly cancer. While Hi-C is the gold standard for mapping chromosomal conformations, it has significant limitations: it requires fixed cells, limiting its capacity for longitudinal monitoring of dynamic chromatin changes. Cell-free DNA (cfDNA), which consists of short DNA fragments released into circulation through apoptosis and necrosis, offers a promising alternative. CfDNA fragmentation patterns are non-random and influenced by underlying epigenetic features, providing a window into chromatin organization in vivo. Here, we hypothesize that the correlation of cfDNA fragmentation patterns between two genomic regions can potentially reflect the 3D chromatin architecture. Since cfDNA fragments in vivo are released from multiple cell types, we generated in situ Hi-C and matched cfDNA whole-genome sequencing data from a xenograft mice model as the training dataset. We trained a contrastive deep learning model to infer Hi-C contact maps directly from cfDNA fragmentation data. The model demonstrated high accuracy in predicting chromatin compartments and topologically associating domains (TADs) from cfDNA fragmentation patterns, outperforming conventional machine learning approaches. These findings suggest that cfDNA fragmentation can enable the non-invasive and longitudinal monitoring of 3D genome aberrations in vivo. Citation Format: Ravi Bandaru, Zhihan Zhou, Hailu Fu, Weimin Wu, Haizi Zheng, Rashmi S. Hegde, Li Wang, Han Liu, Yaping Liu. Predicting chromatin organization from cell-free DNA fragmentation patterns [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 3674.
Abstract 3176: CD19/CD22 bispecific CAR-T cells are effective in CD19 loss B-cell tumor models
Authors: Jiao Jiao
Journal: Cancer Research (2025)

Abstract Background: Chimeric antigen receptor T (CAR-T) cell therapy targeting CD19 can significantly improve the long-term survival rate of patients with relapsed or refractory leukemia. However, CD19 absence or loss leads to resistance of the B-lymphoblastic leukemia cells to CD19 CAR-T cells and the patients will relapse. To solve the problem, we developed bispecific CAR-T cells that target CD19 and CD22 and evaluated their antitumor effects. Methods: The CD19/CD22 bispecific CAR-T cells were generated through the transduction of lentiviruses that simultaneously carry the genes for both CD19 CAR and CD22 CAR, including an anti-CD19 scFv, an anti-CD22 scFv, a CD8 hinge region, a CD8 transmembrane region, a 41BB intracellular region and a CD3ζ intracellular region. In vitro tumor killing assay on NALM6 and Ramos cells and in vivo efficacy studies on Ramos cell line-derived xenografts (CDX) were performed. Results: In in vitro studies, the CD19/CD22 CAR-T cells killed wild-type (WT) NALM6 and WT Ramos cells effectively like CD19 CAR-T; the CD19/CD22 CAR-T cells but not CD19 CAR-T cells killed NALM6 cells with loss of CD19 protein but expression of CD22 protein (CD19-CD22+) and CD19-CD22+ Ramos cells effectively. In in vivo studies, the CD19/CD22 CAR-T cells significantly prolonged the survival of mice bearing CD19-CD22+ Romas cells than CD19 CAR-T. Conclusion: The CD19/CD22 bispecific CAR-T cells effectively kill B-cell tumors with CD19 loss both in vitro and in vivo, which will have a superior therapeutic effect on patients with relapse due to loss of CD19 protein. Citation Format: Jiao Jiao. CD19/CD22 bispecific CAR-T cells are effective in CD19 loss B-cell tumor 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 3176.