tbuckley/cabot-search huggingface dataset:
Abstract 6013: Bi-specific complement engagers (BiCEs) - A novel platform for the potentiation of therapeutic antibodies based on effective complement engagement through C1q
Authors: Mikael Winkler, Dennis Pedersen, Heidi Gytz, Troels Kjær, Nina Dybdal, Alex Ferapontov, Sara Dam, Laust Bavnhøj, Sofia Mølgaard, Pascal Merchiers, Mikkel Wandahl Pedersen, Nick Laursen
Journal: Cancer Research (2025)

Abstract The complement system is a crucial component of the innate immune response, enhancing the body's ability to clear pathogens and damaged cells. It facilitates immune defense mechanisms by promoting inflammation, opsonization, and direct lysis of target cells through the formation of membrane attack complexes (MACs). However, therapeutic antibodies designed to exploit complement-mediated cytotoxicity have faced limitations, including dependence on antigen density, structural constraints related to antibody binding orientation, and the inhibition of complement activation by regulatory molecules expressed on target cells. To address these challenges, we developed a modular IgG-based bispecific antibody platform that engages the complement-initiating protein C1q by fusing anti-C1q variable heavy chain domains (VHHs) to either the heavy or light chains of IgGs. In this study, we present data demonstrating the broad applicability of our platform by enhancing existing complement-deficient antibodies that target a diverse range of clinically relevant tumor antigens with C1q engagers. The resulting bispecific complement engagers (BiCEs) effectively engage C1q and induce robust complement-dependent cytotoxicity (CDC) against cancer cell lines expressing varying levels of target antigens with superior efficacy compared to competing technologies. Moreover, the BiCE molecules retain binding to the neonatal Fc receptor (FcRn) and Fc gamma receptors (FcγRs), resulting in an extended half-life and preservation of secondary effector functions such as antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Our findings suggest that effective activation of the complement system through complement engagers offers a promising alternative to antibody-drug conjugates (ADCs) and T-cell therapies, providing an opportunity to target antigens with lower tumor specificity and potentially expanding therapeutic options for patients with cancer. Citation Format: Mikael Winkler, Dennis Pedersen, Heidi Gytz, Troels Kjær, Nina Dybdal, Alex Ferapontov, Sara Dam, Laust Bavnhøj, Sofia Mølgaard, Pascal Merchiers, Mikkel Wandahl Pedersen, Nick Laursen. Bi-specific complement engagers (BiCEs) - A novel platform for the potentiation of therapeutic antibodies based on effective complement engagement through C1q [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 6013.
Abstract 6009: BGB-B2033, a novel 4-1BB/GPC3 bispecific antibody, exhibits potent in vitro and vivo antitumor activity in preclinical models
Authors: Jie Li, Xi Yuan, Ruyue Ji, Chang Song, Yanwen Ma, Yuan Zhao, Yue Cao, Xinyi Liang, Yilu Zhang, Jingjuan Sun, Xiangli Ma, Lingmin Zheng, Beibei Jiang, Xiaomin Song, Yu Shen, Lai Wang
Journal: Cancer Research (2025)

4-1BB (CD137) is a key costimulatory immunoreceptor expressed on activated T-cells and natural killer cells, making it a promising therapeutic target in cancer. Glypican-3 (GPC3), a membrane-bound heparan sulfate proteoglycan, is overexpressed in approximately 70% to 80% of hepatocellular carcinomas, and extensively expressed in a variety of other solid tumors. GPC3 is recognized as an attractive drug target in precision cancer therapy as it is highly expressed in multiple tumors while minimally expressed in adult normal tissues. BGB-B2033 is a novel immunoglobulin G (IgG)-based bispecific antibody targeting 4-1BB and GPC3 and is under clinical development for the treatment of advanced or metastatic solid tumors in humans. BGB-B2033 binds to its target proteins with high specificity and affinity. Potent and GPC3-dependent functional activities were demonstrated using peripheral blood mononuclear cell (PBMC)-based immune cell activation and cytotoxicity assays. In humanized 4-1BB knock-in mice bearing human GPC3-expressing tumors, BGB-B2033 exhibited potent, dose-associated single-agent efficacy in Hepa1-6/hGPC3 orthotopic tumor model, as well as synergistic antitumor activity in combination with antiPD-1 antibody. In conclusion, BGB-B2033 is a potent therapeutic agent with strong anti-tumor activity in both in vitro and in vivo studies. The phase 1 study of BGB-B2033, alone or in combination with Tislelizumab is ongoing (NCT06427941). Citation Format: Jie Li, Xi Yuan, Ruyue Ji, Chang Song, Yanwen Ma, Yuan Zhao, Yue Cao, Xinyi Liang, Yilu Zhang, Jingjuan Sun, Xiangli Ma, Lingmin Zheng, Beibei Jiang, Xiaomin Song, Yu Shen, Lai Wang. BGB-B2033, a novel 4-1BB/GPC3 bispecific antibody, exhibits potent in vitro and vivo antitumor activity in preclinical 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 6009.
Abstract 6183: Social determinants and survivorship care among Black women breast cancer survivors in Maryland
Authors: Lensa S. Keno, Camryn Mae Cohen, Kate E. Dibble, Kala Visvanathan, Avonne E. Connor
Journal: Cancer Research (2025)

Abstract Purpose: Limited research has examined the impact of social determinants of health (SDOH) on survivorship care experiences exclusively among Black breast cancer (BC) survivors who face survival disparities due their high prevalence of obesity, comorbidities, and inequities in access and quality of care. Survivorship care experiences among Black BC survivors should be examined to identify potential interventions to improve health outcomes. The goal of this study is to test the feasibility of establishing a state-wide cohort study of Black BC survivors residing in Maryland to address this research gap. Methods: This study will recruit 350 Black women BC survivors, aged ≥18 years, and diagnosed with stage I-III primary BC who have completed recommended adjuvant treatment including surgery, chemotherapy, and/or radiation. Recruitment approaches include targeted Facebook ads, outreach to previous study participants, and mailed recruitment letters from the Maryland Cancer Registry (MCR). Participants complete a 30-40-minute online survey, covering demographic and lifestyle factors, clinical and SDOH characteristics, and survivorship care questions. The study also pilots medical record abstractions with the MCR for cancer characteristics and the state designated health-information exchange, Chesapeake Regional Information System for Patients (CRISP), for follow-up care. Results: Recruitment began in July 2024, and by September 2024, 61 self-reported Black participants with a prior diagnosis of BC have completed the survey. The average age at survey is 58.96 (standard deviation (SD)= 11.84)) years, with an average age at diagnosis of 46.42 (SD=13.35) years. 40% are married/living as married, 36.7% are college graduates, all have health insurance, and only 20% reported household incomes &amp;lt;$40, 000/year. Almost half of the survivors self-reported being diagnosed with stage 1 BC (45.9%), followed by 31.1% stage 2, 18% stage 3, and 4.9% unknown stage. The most common self-reported comorbidities include hypertension (39.3%), diabetes (16.7%), and obesity (12.3%). Related to care, 83.3% have a family doctor, and 73.8% received a treatment summary. Additionally, 56.1% and 54.4% consented to medical record linkages with MCR and CRISP, respectively. Recruitment is ongoing. Conclusion: This study will inform future interventions by identifying disparities in survivorship care experiences among Black BC survivors and evaluating the impact of this care on health outcomes. Citation Format: Lensa S. Keno, Camryn Mae Cohen, Kate E. Dibble, Kala Visvanathan, Avonne E. Connor. Social determinants and survivorship care among Black women breast cancer survivors in Maryland [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 6183.
Abstract 6188: Evaluating impact and progress in the iCCaRE consortium for Black men’s approach to reducing prostate cancer disparities
Authors: Ivey Breland, Ernest Kaninjing, Damian Francis
Journal: Cancer Research (2025)

Abstract The purpose of the Inclusive Cancer Care Research Equity for Black men (iCCaRE) Consortium is to address prostate cancer disparities impacting Black men through collaborative research, education, and advocacy. This study evaluates the progress of iCCaRE in achieving its core objectives across five pilot projects supported by multi-institutional partners. Specifically, iCCaRE aims to expand research infrastructure, develop culturally tailored interventions using artificial intelligence to address social determinants of health, explore modifiable social-biological factors affecting patient outcomes, and provide extensive research training for underrepresented minority scientists and advocates. Our methodology involved the creation and implementation of a comprehensive data collection tool via Qualtrics to assess activity outcomes across the Consortium. This tool enabled standardized reporting on publications, grants awarded, media reach, community impact, and additional metrics tied to scientific productivity and partnership engagement. Unpublished data collected this year indicate substantial progress, including an increase in collaborative research outputs, expanded access to prostate cancer care resources, and enhanced engagement with both clinical and community-based partners. These findings underscore the Consortium’s effectiveness in fostering scientific collaboration, developing targeted interventions, and creating infrastructure to support sustainable improvements in prostate cancer outcomes for Black men. These accomplishments provide a strong foundation for iCCaRE’s transition into Phase 2, with plans to deepen community engagement, expand research training, and enhance data-driven insights through advanced analytics. Citation Format: Ivey Breland, Ernest Kaninjing, Damian Francis. Evaluating impact and progress in the iCCaRE consortium for Black men’s approach to reducing prostate cancer disparities [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 6188.
Abstract 3107: Nuciferine inhibits proliferation, invasion, and migration of colorectal cancer cells via the RBM15-JAG2 axis
Authors: KaiHe Zhu, JiaPeng RU, Yichen Zhang, Fangyue Guo, Mengying Liu, Shize Xiao, Xufeng Wang, Jing Wu, Peizhi Ma, Pei Li, Shanfeng Zhang
Journal: Cancer Research (2025)

Background: Colon cancer is the third most common cancer globally, with high incidence and mortality rates. Dietary supplementation therapy, due to its safety, painlessness, high patient acceptance, and practical efficiency, often becomes an adjunctive treatment for colon cancer. Therefore, developing new health foods and exploring new treatment mechanisms are of great significance for the adjuvant treatment of colon cancer. Methods: This study investigated the effects of nuciferine treatment and RBM15 inhibition on the m6A modification of JAG2 using MeRIP-qPCR and actinomycin D experiments. Additionally, the impact on the biological behavior of colorectal cancer cells was assessed through plate colony formation assays, scratch assays, Transwell assays, and Western blot analyses. Results: In this study, through transcriptome sequencing, RBM15 was discovered as a potential target of Nuciferine. The RBM15/JAG2 regulatory axis was found through bioinformatics analysis. Through total m6A detection, MeRip-qPCR, and actinomycin D experiments, it was confirmed that Nuciferine inhibits colon cancer by suppressing the m6A modification of JAG2 by methyltransferase RBM15. Additionally, plate colony experiments, scratch experiments, Transwell experiments, and Western blot experiments demonstrated that Nuciferine can inhibit the proliferation, invasion, and metastasis of colon cancer. In vivo experiments showed that Nuciferine has the effect of inhibiting the proliferation and metastasis of colon cancer. Conclusion: The results of this study indicate that nuciferine inhibits the proliferation, invasion, and migration of colorectal cancer cells by regulating RBM15 expression to mediate JAG2 m6A methylation. Therefore, Nuciferine is an ideal health food for adjuvant treatment of colon cancer. Citation Format: KaiHe Zhu, JiaPeng RU, Yichen Zhang, Fangyue Guo, Mengying Liu, Shize Xiao, Xufeng Wang, Jing Wu, Peizhi Ma, Pei Li, Shanfeng Zhang. Nuciferine inhibits proliferation, invasion, and migration of colorectal cancer cells via the RBM15-JAG2 axis [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 3107.
Abstract 3140: Preclinical development of YL242, a non-internalized antibody-drug conjugate (ADC) targeting soluble VEGF for treatment of solid tumors
Authors: Tongtong Xue, Wei Lian, Qing Zong, Chun Deng, Qigang Liu, Peng Zou, Jiaqiang Cai
Journal: Cancer Research (2025)

Traditional ADC technologies require overexpressed targets, high internalization and efficient intracellular processing. To this end, a non-internalized antibody-drug conjugate (ADC) targeting soluble VEGF was developed using MediLink’s TMALIN® platform. VEGF is overexpressed in virtually all human tumors and contributes to key aspects of tumorigenesis and angiogenesis. YL242 incorporates an anti-VEGF antibody, protease-cleavable tripeptide linker and novel DNA topoisomerase I inhibitor. It introduces a novel cleavage mechanism that occurs in the tumor microenvironment while stable during systemic circulation. YL242 is designed to leverage anticancer activity through both anti-angiogenesis by the VEGF antibody and the cytotoxicity of the extracellularly released payload. The linker of YL242 can be enzymatically cleaved by enzymes in TME (tumor microenvironment) to release payload C24, subsequently inducing cytotoxic effects to kill cancer cells. Significant dose-dependent antitumor effects, including complete tumor regressions were observed in tumor xenograft mouse models. The stability of YL242 has been demonstrated by incubation with various plasmas under physiological conditions. This high stability was further evidenced by the pharmacokinetic profiles in non-human primate (NHP) studies, where both the ADC and TAb curves are overlapped. YL242 demonstrated promising safety profiles in pivotal non-human primate (NHP) toxicity studies with no drug-related adverse effects observed. In summary, VEGF-targeted ADC YL242 synergistically combines both antitumor activity of cytotoxic payload and anti-angiogenesis effect of antibody and demonstrated both antitumor efficacy and safety. Consequently, YL242 holds promise for further development in the treatment of cancer patients. Citation Format: Tongtong Xue, Wei Lian, Qing Zong, Chun Deng, Qigang Liu, Peng Zou, Jiaqiang Cai. Preclinical development of YL242, a non-internalized antibody-drug conjugate (ADC) targeting soluble VEGF for treatment of solid tumors [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 3140.
Abstract 3695: A mechanistic model of ctDNA shedding and its relevance for clinical interpretation
Authors: Thomas Rachman, Patrick Wagner, William LaFramboise, David Bartlett, Russell Schwartz, Oana Carja
Journal: Cancer Research (2025)

Abstract Circulating tumor DNA (ctDNA) in plasma is a key biomarker of tumor dynamics, yet the quantitative relationship between ctDNA levels and clinical variables—such as tumor volume, vascularization, and cell death—remains unclear. The release of ctDNA is thought to depend on cell death mechanisms and the transport of extracellular tumor DNA (excDNA) to blood vessels. We hypothesized that ctDNA concentrations are modulated by the interplay between proximity to blood vessels and excDNA transport kinetics. To test this hypothesis, we develop a spatial mechanistic model to first predict hypoxia-mediated cell death based on blood vessel distribution and then assess the amount of excDNA reaching blood vessels after release, incorporating diffusion and degradation parameters within empirically plausible ranges. In our model, we find that ctDNA concentration in plasma depends on both vascularization and transport dynamics. For example, when diffusion dominates, ctDNA yield is high, and increasing hypoxic cell death from 0 to 80% leads to a tenfold increase in ctDNA. When degradation dominates, ctDNA yield is much lower and the same change in hypoxia results in a tenfold decrease. When both terms are relevant, ctDNA depends nonlinearly on vascularization. These findings suggest that the relationship between blood vessel proximity and ctDNA is highly sensitive to excDNA transport dynamics, underscoring the importance of experimental validation of key parameters, which may vary significantly according to site and release mechanism. Citation Format: Thomas Rachman, Patrick Wagner, William LaFramboise, David Bartlett, Russell Schwartz, Oana Carja. A mechanistic model of ctDNA shedding and its relevance for clinical interpretation [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 3695.
Abstract 6011: Neoantigen peptide-loaded anti-CD40-spycatcher antibody as a novel cancer vaccine platform
Authors: Xiaoying Cai, Dahee Jung, Seung-Oe Lim, Steve Seung-Young Lee
Journal: Cancer Research (2025)

Abstract Precision cancer therapy opened up an attractive strategy by therapeutic vaccines targeting neoantigens. Neoantigens are immunogenic and HLA-bound epitopes capable of activating helper and cytotoxic T lymphocytes and not subject to immunological tolerance. However, personalized peptide-based cancer vaccines still have the limitations to formulate and deliver. For example, most vaccine technology was initially based on the use of adjuvants (e.g., alum), which only provides moderate therapeutic effects. To address these issues, we utilize the engineered anti-CD40 agonistic antibody expressing Spy-Catcher003 (αCD40-SC) as a novel antigen presenting cells (APCs)-targeted peptide vaccine delivery platform for effective cancer immunotherapy. Since targeting and activating the CD40 receptor on APCs via anti-CD40 agonistic antibody has been shown to elicit superior T cells priming and boost antigen-specific CD8+ T. Besides, the use of SpyCatcher003, which is a 113-residue protein with reactive Lys31, could trigger spontaneous and irreversible amidation reaction with SpyTag003. SpyTag003/SpyCatcher003 is a protein coupling approach, which can form an intermolecular isopeptide bond between Lys31 and Asp117. Moreover, the protein pair can react with a rate of 5.5 x 105 M-1 s-1, which is helpful for potential therapeutic application.Therefore, we hypothesize the efficient and specific delivery, accomplished via SpyCatcher003-expressed anti-mouse CD40 agonistic antibody and SpyTag003-conjugated neoantigen peptide, will ensure the present of neoantigens to T cells and elicit robust and durable specific CD8+ T cell response. Our goal is to directly deliver neoantigen peptide-loaded αCD40-SC to APCs in draining lymph nodes (dLN) as a therapeutic vaccine. Citation Format: Xiaoying Cai, Dahee Jung, Seung-Oe Lim, Steve Seung-Young Lee. Neoantigen peptide-loaded anti-CD40-spycatcher antibody as a novel cancer vaccine platform [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 6011.
Abstract 1305: Brief pulses of high-level fluid shear stress enhance metastatic potential and rapidly alters the metabolism of cancer cells
Authors: Amanda N. Pope, Devon L. Moose, Sujata Birua, Guy O. Hudson, Hank Weresh, Patrick Breheny, Michael D. Henry
Journal: Cancer Research (2025)

Abstract During their journey through the circulation, circulating tumor cells (CTCs) face challenges to their survival including mechanical stresses related to their dynamic fluid microenvironment and oxidative stress related to their detached cell state. Recently, we identified a mechano-adaptive response to transient fluid shear stress (FSS) exposure that enables cancer cells to survive mechanical destruction in the circulation and found that it involves an increase in the activation of RhoA-actomyosin signaling (Moose et al., Cancer Cell 2020). Because RhoA is likely to influence other phenotypes involved in metastasis, such as invasiveness, we hypothesized that activation of RhoA by FSS may promote metastatic behavior in CTCs. Here we find that cancer cells (PC-3, MDA-MB-231, Myc-CaP) exposed to brief pulses of high-level FSS (∼1msec, τ =750-6400 dynes/cm2) exhibit enhanced invasiveness (dependent on RhoA) and anchorage-independent proliferation in vitro and enhanced metastatic colonization/tumor formation in vivo as compared to static controls. To investigate how exposure to FSS confers these phenotypes, we conducted transcriptomic and metabolomic profiling. Transcriptomic analysis at 3, 6, and 24h post FSS exposure revealed enrichment of gene expression involved in oxidative phosphorylation. Consistent with this, we found elevated oxygen consumption of cells exposed to FSS at 24h. Metabolomic profiling of cells immediately after exposure to FSS demonstrated rapid energy utilization consistent with actin remodeling and contractility as well as depletion of amino acids acids associated with the folate pathway. Cells exposed to FSS exhibit a reduced reactive oxygen species burden as compared to static controls. Consistent with the hypothesis that FSS-dependent activation of the folate pathway reduces oxidative burden in cells exposed to FSS, we found that exposure of cancer cells with the folate inhibitor methotrexate, sensitized those cells destruction by FSS. Taken together our data indicate that cancer cells that survive exposure brief pulses of FSS are primed for metastatic colonization in part through rapid metabolic programming that enables them to withstand oxidative stress associated with cell detachment. Thus, some CTCs may derive an unexpected survival benefit through encountering FSS in the circulation. Citation Format: Amanda N. Pope, Devon L. Moose, Sujata Birua, Guy O. Hudson, Hank Weresh, Patrick Breheny, Michael D. Henry. Brief pulses of high-level fluid shear stress enhance metastatic potential and rapidly alters the metabolism of cancer 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 1305.