tbuckley/cabot-search huggingface dataset:
Abstract 323: Preclinical evaluation of SDV2102, a novel PSMA-targeting DAR1 ADC for mCRPC treatment
Authors: Damien Dattler, Fabian Schlimpen, Constantin Semenchenko, Oleksandr Koniev, Sergii Kolodych
Journal: Cancer Research (2025)

Abstract Metastatic castration-resistant prostate cancer (mCRPC) presents a significant therapeutic challenge due to limited treatment options. Prostate-specific membrane antigen (PSMA) is overexpressed in mCRPC tumors, making it a viable target for antibody-drug conjugates (ADCs). We developed SDV2102, a novel PSMA-targeting ADC designed to enhance tumor penetration and efficacy. SDV2102 utilizes a novel anti-PSMA antibody, D10, selected for its superior antigen-binding properties. The D10 antibody is conjugated with monomethyl auristatin E (MMAE), a tubulin-binding cytotoxic agent to which mCRPC tumors are inherently more sensitive than to topoisomerase I inhibitors. Notably, SDV2102 has a drug-to-antibody ratio (DAR) of 1, allowing for higher dosing and increased efficacy without proportional increases in systemic toxicity, thereby improving the therapeutic index. In vivo efficacy was assessed using the C4-2 cell-derived xenograft (CDX) model, characterized by high PSMA expression. SDV2102 demonstrated significantly greater anti-tumor efficacy than classical DAR4 ADCs constructed with either the generic J591 antibody or the D10 antibody when administered at equivalent doses of MMAE. Additionally, SDV2102 showed potent activity in patient-derived xenograft (PDX) models with low to moderate PSMA expression levels, with some tumors expressing as few as 25, 000 receptors per cell. This indicates that SDV2102 may be effective across a spectrum of PSMA expression in mCRPC tumors. Pharmacokinetic studies in rats revealed that SDV2102 has a favorable profile, closely mirroring that of the unconjugated D10 antibody, suggesting maintained antibody-like characteristics in circulation. Dose-response studies in the C4-2 model identified a minimum effective dose of 2.5 mg/kg. Toxicology studies in non-human primates showed no major toxicities at doses up to 24 mg/kg, with the maximum tolerated dose (MTD) not reached, indicating a wide therapeutic window. SDV2102 achieved a therapeutic index of 38, representing a substantial safety margin. These preclinical results support the advancement of SDV2102 into clinical trials as a promising therapeutic candidate for the treatment of mCRPC. Citation Format: Damien Dattler, Fabian Schlimpen, Constantin Semenchenko, Oleksandr Koniev, Sergii Kolodych. Preclinical evaluation of SDV2102, a novel PSMA-targeting DAR1 ADC for mCRPC treatment [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 323.
Abstract 321: BTE-EN1, a novel acting heterobifunctional compound inhibiting bone destruction by established prostate cancer bone metastasis
Authors: Fangfang Qiao, Ryan Gordon, Abhinandan Pattanayak, Katelyn O’Neill, Weining Chen, Prathap R. Mukthapuram, Amar Natarajan, Raymond Bergan
Journal: Cancer Research (2025)

Bone destruction by prostate cancer (PCa) metastasis is a major cause of morbidity and mortality. In order to destroy bone, PCa and bone cells stimulate each other in a process that requires their coordinated movement within bone itself. To therapeutically inhibit this process, we synthesized the first-in-class heterobifunctional compound, BTE-EN1. One group is a selective inhibitor of cancer cell motility, discovered by us (Nature Communications 2018). It is chemically coupled to a bisphosphonate group, which binds to bone mineral and enables targeted delivery of the therapeutic to bone-destructive lesions. We sought to test whether BTE-EN1 would be active against well-established bone-destructive PCa metastasis and to evaluate its potential as a therapeutic. We used the state-of-the-art caudal artery injection model to selectively deposit human PCa cells into the long bones of the leg in mice and let them grow for two weeks, thus emulating the scenario of established disease in patients. We then began weekly administration of BTE-EN1 for six weeks, quantified bone destruction by CT imaging and demonstrated a significant decrease in bone destruction by 62%, compared to control. In a separate study, BTE-EN1 treatment prior to intra-cardiac injection of PCa cells led to dose-dependent significant prolongation of life, a finding not seen with bisphosphonate and denosumab therapies. Comprehensive in vitro studies demonstrate that BTE-EN1 retains the cellular and molecular pharmacologic and pharmacodynamic properties of its two functional groups. BTE-EN1 exhibited no toxicity when mice were treated at a dose 4000-fold higher than that showing efficacy and lacked toxicity in the NCI-60 cell line panel screen. Additional studies supporting translation to the clinic include non-interference with therapy used to treat advanced PCa, as well as inhibition of cell motility across a panel of human cancer cell types associated with bone destruction. In conclusion, BTE-EN1 is a first-in-class highly active heterobifunctional compound that inhibits bone destruction in established PCa bone metastasis and is well tolerated. Our data strongly suggests that BTE-EN1 has high potential for translation into humans and constitutes a novel therapeutic strategy. Citation Format: Fangfang Qiao, Ryan Gordon, Abhinandan Pattanayak, Katelyn O’Neill, Weining Chen, Prathap R. Mukthapuram, Amar Natarajan, Raymond Bergan. BTE-EN1, a novel acting heterobifunctional compound inhibiting bone destruction by established prostate cancer bone 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 321.
Abstract 481: Development of a rapid method for the detection of neutralizing antibodies in sera of primates for viral gene therapy stratification
Authors: Gregor Sommerkamp, Eva M. Egenter, Katharina Schaich, Daniel Feger, Sebastian Dempe, Jan E. Ehlert
Journal: Cancer Research (2025)

Abstract Gene therapeutical intervention using viral vectors is becoming increasingly relevant for the treatment of various diseases, including cancer. A critical factor for a successful viral therapy is that the patient has not previously developed neutralizing antibodies to the respective viral serotype in the context of a naturally occurring anti-infection immune response. Such antibodies would impose the risk to neutralize and thus jeopardize the intended therapeutic response. This is especially relevant in therapies with adeno-associated virus (AAV), as immunity against AAV-serotypes is very common. We here report on the development and validation of a straightforward method to functionally detect neutralizing antibodies in primate sera, employing a transduction method on a human cell line using AAVs of different serotype coding for an easily detectable transgene. The reported methodology will be helpful for the stratification of primates and patients exploiting their sera for the prevalence of neutralizing antibodies prior to the initiation of the AAV treatment. In addition, our assay has the potential to be applied to other viral treatment strategies also. Citation Format: Gregor Sommerkamp, Eva M. Egenter, Katharina Schaich, Daniel Feger, Sebastian Dempe, Jan E. Ehlert. Development of a rapid method for the detection of neutralizing antibodies in sera of primates for viral gene therapy stratification [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 481.
Abstract 353: Preclinical development of MHB048C: A novel anti-PSMA ADC with a potent topoisomerase I inhibitor
Authors: Yile Chen, Ao Li, Bo Liu, Liyuan Zhu, Xiang Meng, Zhili Yao, Yan Wang, Xialian Weng, Xuefeng Zhu, Shiyu Zhou, Junwei Shi, Guoqing Cao
Journal: Cancer Research (2025)

Abstract Prostate-specific membrane antigen (PSMA), a type II transmembrane glycoprotein, is highly and specifically expressed in prostate cancer while showing limited expression in normal tissues. The FDA’s approval of (177) Lu-PSMA-617 has validated PSMA as a therapeutic target for treating metastatic castration-resistant prostate cancer (mCRPC). Here, we present the development and preclinical characterization of MHB048C, a novel PSMA specific antibody-drug conjugate (ADC). MHB048C comprises a human IgG1 antibody against PSMA, conjugated to the SuperTopoiTM payload, a novel DNA topoisomerase I inhibitor that is 3∼5 times more potent than DXd. The drug-antibody ratio is approximately 4.0. Fc function was silenced to minimize nonspecific ADC uptake, and the linker was designed to enhance hydrophilicity and prevent the retro-Michael reaction, improving plasma stability. The antibody preferentially binds to the PSMA dimer rather than the monomer, as only dimers display the native conformation. MHB048C showed strong binding affinity in protein and cell-level assays and was efficiently internalized by LNCaP cells, reaching an internalization rate of ∼70% within 1 hour. It exhibited potent cytotoxicity in PSMA-positive prostate cancer cell lines with varying PSMA expression levels and demonstrated significant antitumor activity in an LNCaP FGC prostate cancer xenograft model. In GLP monkey studies, MHB048C exhibited a favorable safety profile with no off-target toxicities. The highest non-severely toxic dose (HNSTD) was determined to be 45 mg/kg Q3W, the maximum dose tested. In conclusion, MHB048C demonstrated potent anti-tumor activity both in vitro and in vivo, along with a favorable safety profile, supporting advancement to clinical development. Citation Format: Yile Chen, Ao Li, Bo Liu, Liyuan Zhu, Xiang Meng, Zhili Yao, Yan Wang, Xialian Weng, Xuefeng Zhu, Shiyu Zhou, Junwei Shi, Guoqing Cao. Preclinical development of MHB048C: A novel anti-PSMA ADC with a potent topoisomerase I inhibitor [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 353.
Abstract 74: Hypoxia-fibrosis cycle in pancreatic tumor microenvironment: Implication for diagnosis and treatment
Authors: Nai-Jung Chiang, Ya-Chin Hou, Jiun-I Lai, Lun-De Liao, Yan-Shen Shan
Journal: Cancer Research (2025)

Pancreatic cancer (PC) is difficult to treat and has the lowest five-year survival rate across the world. PC are characterized by a dense fibrotic stroma composed of abundant cancer-associated fibroblasts (CAFs) and excessive extracellular matrix (ECM), which creates a pathological barrier that impedes drug delivery to tumors, leading to suboptimal treatment efficacy and resistance to current therapeutics. Like a vicious cycle, hypoxia-fibrosis cycle consists of dynamic cancer cell-CAF interactions. Currently, most clinical therapeutics aim at tumor cells while overlooking the surrounding tumor microenvironment (TME). The TME comprises all of the physiological and biochemical elements, including, but not limited to, the ECM, CAFs, cancer-associated immune cells, and the hypoxic and acidic environment. Therefore, we aim to investigate intratumor heterogeneity of PC and figure out the tumor- and TME-driven signaling by using multi-omics analysis. The data obtained from bulk and single-cell RNA sequencing, spatial transcriptomics, and tissue microarrays show that hypoxia levels were positively correlated with tumor fibrosis. Hypoxia-fibrosis cycle modulates PC progression and pro-tumoral inflammatory microenvironment, which was associated with activation of hypoxia, KRAS, mTORC1, and inflammatory response pathways. This cycle acts as a poor prognostic indicator in patients with PC. We also established a three-dimensional cell culture model mimicking cancer cell in hypoxia-fibrosis environment to validate the impacts of hypoxia-fibrosis cycle on promoting the malignant phenotype of PC cells. A dual-modality ultrasound (US) and photoacoustic (PA) real-time imaging system is demonstrated to assess tissue oxygen saturation dynamics as well as tumor fibrosis in an orthotopic PC mouse model with/without irinotecan or nanoliposomal irinotecan treatment and highlights the potential for evaluating the efficacy of cancer therapies in preclinical settings. Our work provides useful information for enhancing the effectiveness of current therapies and may have the potential to develop new precision medicines. Citation Format: Nai-Jung Chiang, Ya-Chin Hou, Jiun-I Lai, Lun-De Liao, Yan-Shen Shan. Hypoxia-fibrosis cycle in pancreatic tumor microenvironment: Implication for diagnosis and treatment [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 74.
Abstract 65: Real time imaging of the non-small cell lung cancer immune microenvironment modulation by low dose photodynamic therapy
Authors: Damien N. Marie, Louis-Emmanuel Chriqui, Alexandros Sifis, Etienne Abdelnour, Michel Gonzalez, Thorsten Krueger, Johanna A. Joyce, Sabrina Cavin, Jean Y. Perentes
Journal: Cancer Research (2025)

Abstract Immune checkpoint inhibitors (ICIs) have significantly improved the outcome of non-small cell lung cancers (NSCLCs). However, cancer response to ICIs occurs in a fraction of patients and correlates with the presence of tumor-infiltrating lymphocytes (TILs). Thus, methods to increase the presence of TILs within lung cancer are urgently needed. Previously, in a murine model of malignant pleural mesothelioma, we described a mechanism by which low dose photodynamic therapy (L-PDT) enhanced the vascular expression of E-selectin which favored TILs recruitment and improved tumor control. Here, we hypothesized that a similar mechanism existed in NSCLC and could be further potentiated by ICIs.We developed a murine model with a chest window allowing real time imaging by two-photon microscopy of lung adenocarcinoma (LUAD, 344-SQ-GFP, KrasG12D; p53R172HΔG mutant) growing in the lungs of C57BL/6-CD2-dsRed transgenic mice. We determined the impact of L-PDT±E-selectin blocking antibodies (EBA) on CD2+TILs recruitment over 30 days. In a separate experiment, we then assessed the impact of L-PDT±EBA on tumor growth, animal survival and spontaneous metastasis development. Finally, we characterized the LUAD immune microenvironment and TILs immune checkpoint expression 1 and 5 days after L-PDT by 16-colors flow cytometry. L-PDT significantly enhanced the recruitment of CD2+TILs, with a significant increase observed at day 1, that lasted up to 20 days post-treatment compared to controls. L-PDT was significantly correlated with improved tumor control (-42%), a significant reduction in metastasis development (-50%) and an increase in animal survival (+26%) compared to the control group. Interestingly, this phenotype was abrogated to control levels when L-PDT was combined with EAB. Further analysis of the tumor immune microenvironment confirmed the recruitment of CD8+ T lymphocytes at both 1- and 5-days following L-PDT with increased PD-1 expression on their surface day 5 post-treatment compared to controls. L-PDT triggers, through vascular E-Selectin, a durable infiltration of NSCLCs by TILs which provide better tumor control, impair metastasis development, and improve animal survival. The increased PD-1 levels on CD8-T cells following L-PDT suggest a favorable combination with PD1/PDL1 inhibitors. Citation Format: Damien N. Marie, Louis-Emmanuel Chriqui, Alexandros Sifis, Etienne Abdelnour, Michel Gonzalez, Thorsten Krueger, Johanna A. Joyce, Sabrina Cavin, Jean Y. Perentes. Real time imaging of the non-small cell lung cancer immune microenvironment modulation by low dose photodynamic 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 65.
Abstract 1065: Exploring differential gene expression in head and neck squamous cell carcinoma using TCGA data
Authors: Donghoon Shin, Ji Hyung Hong
Journal: Cancer Research (2025)

Abstract Introduction: The prognosis for head and neck squamous cell carcinoma (HNSCC) has shown limited advancements, and our understanding of how gene expression relates to patient outcomes remains unclear. With advancements in bioinformatics, the characterization of molecular abnormalities and the identification of prognostic signatures have become increasingly important for risk stratification, survival prediction, and treatment management of HNSCC patients. However, due to its lower prevalence, challenges remain in utilizing genetic markers to better understand prognosis. In this study, we performed a differential gene expression analysis (DEGs) to identify genes associated with overall survival. Methods: RNA sequencing data from TCGA, including gene expression profiles and clinical information (tumor stage, overall survival), were analyzed to identify DEGs in HNSCC. DEGs associated with overall survival were identified using the R package DESeq2, and an integrated prognostic signature was developed. Kaplan-Meier survival analysis and log-rank tests were used to evaluate the prognostic value of DEGs, stratifying patients into high- and low-risk groups based on expression levels. A multivariate Cox regression analysis was performed to calculate the hazard ratios (HRs) for each gene, which were then used to construct a risk score. Results: RNA expression data from 521 HNSCC patients were obtained from the TCGA database, comprising 111 early-stage (stage I, II) and 410 advanced-stage (stage III, IV) patients. DEG analysis comparing early-stage and advanced-stage tumors identified 51 genes, including 45 upregulated and 6 downregulated genes. Among these 51 genes, patients were stratified into high- and low-expression groups for each of the genes based on median expression levels. Kaplan-Meier survival analysis revealed that three genes—BRDT (p = 0.0870), ZFP42 (p = 0.0213), and FDCSP (p = 0.0343)—were significantly associated with overall survival. The HRs obtained from the multivariate Cox regression model are as follows: BRDT (HR = 1.51, 95% CI: 1.11-2.06, p = 0.009), ZFP42 (HR = 1.43, 95% CI: 1.05-1.94, p = 0.022), and FDCSP (HR = 0.72, 95% CI: 0.53-0.98, p = 0.035). Conclusions: The study identified a novel 3-gene signature that can stratify HNSCC patients into distinct risk groups based on overall survival. Through DEG analysis, key genes linked to the prognosis of HNSCC were identified, providing valuable insights into the prognostic factors of the disease. Citation Format: Donghoon Shin, Ji Hyung Hong. Exploring differential gene expression in head and neck squamous cell carcinoma using TCGA data [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 1065.
Abstract 1040: Voices of resilience: Analysing #MetastaticBreastCancer content on TikTok
Authors: Nina Morena, Carla Herman, Jillian Schneidman, Eric Belzile, Ari N. Meguerditchian
Journal: Cancer Research (2025)

INTRODUCTION: Young women with metastatic breast cancer (YWMBC) have unique biopsychosocial challenges, for which they often turn to social media for information and support. The aim of this study is to understand YWMBC engagement on TikTok and analyze content about MBC. METHODS: Videos tagged with #metastaticbreastcancer on TikTok were collected in 07/24. Reviewers gathered video characteristics: username, user profile, caption, length, date posted, number of followers, likes, views, shares, comments, and presence of sponsorship. Creator demographics were noted. Explanations, communication style, themes, and topics discussed were assessed. Spearman’s correlation coefficient was calculated between variables. RESULTS: 336 English language TikToks were included. Most videos (41%) were posted in 2024, 97% were from individuals. 1% included sponsorship. Average video length was 1:46 minutes. 161 used music. Mean follower number was 61,927 (SD 350,900). Mean number of views, likes, and comments was 209,882 (SD 625,961), 15,541 (SD 134,070), and 622 (SD 3899), respectively. The majority of videos were filmed at home (56%), specifically in the bedroom. 21% were filmed in a hospital setting. Average age at diagnosis was 31.4 years old (SD 4.3). Emotion was explicitly present in 24% of videos. Topics discussed included: daily life with MBC (70%), diagnosis (42%), treatment options (38% systemic, 26% surgery and 16% radiation). Themes are addressed in Table 1. Most relevant correlations for engagement (likes, views) included display of surgical scars, explicit expression of emotions, and diagnosis story. Predictors specific to more comments included fear of recurrence, grief and motherhood. CONCLUSION: TikToks from YWMBC present personal narratives of the daily experience of MBC. They are minimally sponsored and generate higher engagement when personal content/emotions are displayed. They may represent a journaling equivalent and could potentially have a beneficial effect on patients. Citation Format: Nina Morena, Carla Herman, Jillian Schneidman, Eric Belzile, Ari N. Meguerditchian. Voices of resilience: Analysing #MetastaticBreastCancer content on TikTok [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 1040.