tbuckley/cabot-search huggingface dataset:
Abstract 1847: Closed-loop drug delivery system to personalize chemotherapy dosing
Authors: Louis DeRidder, Kyle Hare, Ted Smierciak, Mia Chao, Aaron Lopes, Josh Jenkins, Nina Fitzgerald, Emmeline MacPherson, Niora Fabian, Josh Morimoto, Jacqueline Chu, Ameya Kirtane, Wiam Madani, Keiko Ishida, Johannes Kuosmanen, Naomi Zecharias, Christopher Colangelo, Hen-Wei Huang, Makaya Chilekwa, Nikhil Lal, Shriya Srinivasan, Alison Hayward, Brian Wolpin, David Trumper, Troy Quast, Douglas Rubinson, Robert Langer, Giovanni Traverso
Journal: Cancer Research (2025)

While most oncologists know that many chemotherapies are dosed on a body surface area (BSA) basis, fewer know that the equations used to estimate BSA are based on a study done over 100 years ago using data from just 9 people. Moreover, two patients with the same BSA can have many factors, such as body composition and genetics, which can impact a drug’s pharmacokinetics and pharmacodynamics, resulting in worse therapeutic outcomes. To solve this problem, we developed a medical device that can personalize the dose of chemotherapy to the patient during an infusion center visit. Our medical device, which we call CLAUDIA (the Closed-Loop AUtomated Drug Infusion regulator) is a closed-loop drug delivery system that measures the concentration of drug and changes the infusion rate in real time to keep the concentration of drug within the therapeutic window. CLAUDIA uses high performance liquid chromatography-mass spectrometry (HPLC-MS) as the sensor, which allows it to be relatively easily translated to control many different drugs, either individually or in a combination chemotherapy regimen. We demonstrate CLAUDIA can control the concentration of 5-fluorouracil (5-FU) in rabbits, which were manipulated to capture the pharmacokinetic variability observed clinically. We then adapted CLAUDIA to also control the concentration of irinotecan, demonstrating its ability to be rapidly translated to additional chemotherapies. Finally, we perform a cost-effectiveness analysis that demonstrates that CLAUDIA is cost-effective compared to the current standard of care for drug dosing of 5-FU (i.e., BSA). Overall, CLAUDIA presents promising medical device that can personalize the dosing of chemotherapy, which may be able to improve the therapeutic outcomes for multiple chemotherapies. Citation Format: Louis DeRidder, Kyle Hare, Ted Smierciak, Mia Chao, Aaron Lopes, Josh Jenkins, Nina Fitzgerald, Emmeline MacPherson, Niora Fabian, Josh Morimoto, Jacqueline Chu, Ameya Kirtane, Wiam Madani, Keiko Ishida, Johannes Kuosmanen, Naomi Zecharias, Christopher Colangelo, Hen-Wei Huang, Makaya Chilekwa, Nikhil Lal, Shriya Srinivasan, Alison Hayward, Brian Wolpin, David Trumper, Troy Quast, Douglas Rubinson, Robert Langer, Giovanni Traverso. Closed-loop drug delivery system to personalize chemotherapy dosing [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 1847.
Abstract 2112: Association between visceral fat obesity and perioperative complications of undernutrition in laparoscopic surgery for colorectal cancer
Authors: Kengo Haruna, Norikatsu Miyoshi, Shiki Fujino, Rie Mizumoto, Rie Hayashi, Mitsunobu Takeda, Yuki Sekido, Tsuyoshi Hata, Atsushi Hamabe, Takayuki Ogino, Mamoru Uemura, Hirofumi Yamamoto, Yuichiro Doki, Hidetoshi Eguchi
Journal: Cancer Research (2025)

Abstract Background: Visceral obesity and malnutrition are each associated with poor prognosis in gastrointestinal cancers. This study investigates the impact of undernutrition combined with visceral obesity on perioperative complications in laparoscopic colorectal cancer surgery. Methods: We retrospectively analyzed 223 colorectal cancer patients who underwent curative laparoscopic resection at our institution between January 2010 and December 2011. Undernutrition was defined as the Geriatric Nutritional Risk Index (GNRI), calculated using the ideal body weight ratio and serum albumin level, with GNRI &amp;lt; 107 indicating undernutrition. Visceral obesity was defined as a visceral fat area (VFA) &amp;gt;100 cm2 at the umbilical level. Patients were divided into two groups: those with both undernutrition and visceral obesity (n=40) and others (n=183). Associations with perioperative complications were analyzed, along with background factors including age, gender, BMI, albumin (Alb), CRP, tumor markers, and other nutritional indices. Additionally, a new nutritional status score for predicting postoperative complications was developed using ROC curve analysis based on easily measurable indicators from blood tests, CT scans, and physical exams. Results: The malnutrition and visceral obesity group showed a significantly higher incidence of Grade 2 or higher perioperative complications compared to the other group (25.0% vs. 10.9%; p = 0.037). Analysis of nutritional and oncological indicators identified age, BMI, VFA, CRP, lymphocyte count, and CA19-9 as associated with postoperative complications. A novel nutritional status score incorporating these factors predicted Grade 2 or higher complications with a sensitivity of 43.0% and a specificity of 83.3%. Conclusions: Undernutrition combined with visceral obesity significantly increased the risk of perioperative complications. Preoperative nutritional interventions to improve patient status may reduce these risks and should be further investigated. Citation Format: Kengo Haruna, Norikatsu Miyoshi, Shiki Fujino, Rie Mizumoto, Rie Hayashi, Mitsunobu Takeda, Yuki Sekido, Tsuyoshi Hata, Atsushi Hamabe, Takayuki Ogino, Mamoru Uemura, Hirofumi Yamamoto, Yuichiro Doki, Hidetoshi Eguchi. Association between visceral fat obesity and perioperative complications of undernutrition in laparoscopic surgery for 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 2112.
Abstract 3621: Geographic and racial disparities in bladder cancer care in the U.S.
Authors: Atreyee Majumder, Daniel Erim, Arveen Kaur, Lisa Dwyer Orr
Journal: Cancer Research (2025)

Abstract Introduction: This study aims to elucidate variations in bladder cancer health outcomes and social determinants of health across diverse geographic regions in the US. It specifically investigates racial disparities in care delays among patients with bladder cancer, identifying critical intervention areas to enhance health equity. Methods: A retrospective database analysis was conducted utilizing Medicare fee-for-service data for patients with bladder cancer diagnosed between January 1, 2021, and December 31, 2022, to measure and compare rates of diagnosis, interventions (surgical or pharmacological), specialist visit, time-to-specialist visit, and diagnosis-to-treatment initiation across US racial and ethnic groups. The reference group for rates was White patients. For example, the diagnosis rate ratio for Black patients was the quotient of diagnosis rates among Black residents and diagnosis rates among White residents diagnosed with bladder cancer during the study period. Diagnosis claims with ICD-10 code C67 and ICD-9 code 188 were used. Medicare patients with at least one year of enrollment were included. Patients were excluded if their first bladder cancer diagnosis was outside the study period. Results: Diagnosis rate ratios were 0.5 for Black patients and 0.4 for Hispanic patients. Intervention rate ratios were 0.9 for Black patients and 0.8 for Hispanic patients. Specialist visit rate ratios were 0.9 for both Black patients and Hispanic patients. Median time-to-specialist visit was 21 days for all patients, while mean (standard deviation) times were 89 (162) days for Black patients, 77 (128) days for Hispanic patients, and 85 (148) days for White patients. Mean (standard deviation) diagnosis-to-treatment initiation were 29 (91) days for Black patients, 33 (94) days for Hispanic patients, and 27 (90) days for White patients; the corresponding 95% confidence interval was (29, 36) and (26, 28) for Hispanic and White patients, respectively. Conclusion: At the national level, diagnosis-to-treatment initiation for bladder cancer was significantly delayed for Hispanic patients and disparities in intervention were identified for Black and Hispanic patients in hotspots of economic inequity. Stakeholders, including population health decision makers, healthcare providers, payers, advocacy groups and policymakers, can use the study findings to design and implement strategies to reduce geographic and racial disparities, foster collaboration among key stakeholders, and improve overall healthcare quality. Citation Format: Atreyee Majumder, Daniel Erim, Arveen Kaur, Lisa Dwyer Orr. Geographic and racial disparities in bladder cancer care in the U.S. [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 3621.
Abstract 2189: A spectral flow cytometry panel and workflow for the reproducible assessment of colorectral tumor immunophenotype in the context of immunotherapies
Authors: Joseph P. Kolb, Kathryn R. Meshaw, Timothy Hutchinson, Karsten Fynboe, Jacob Hauser, William D. Culp, Beth A. Hollister
Journal: Cancer Research (2025)

Multiparameter flow cytometry analysis of immune cells within solid tumors has provided insight into the mechanism of action of novel immunotherapies, but challenges exist regarding the interpretation of data stemming from variation in sample processing, selection of optimal combinations of fluorochrome-conjugated antibodies, and population gating strategy. Here we present a 20-color spectral flow cytometry backbone panel and gating scheme that can be applied to syngeneic colorectal tumor samples from different mouse strains with minimal manual adjustment. Using the CT26 and MC38 subcutaneous implant models in BALB/c and C57BL/6 mice, respectively, we tested the ability of our panel and workflow to identify changes in tumor immune cell populations after treatment with the immune checkpoint inhibitors (ICIs) anti-PD-1 and/or anti-CTLA-4 in two independent experiments. Our panel identified differences between the models, largely confined to protein surface expression within the monocyte, macrophage, and dendritic cell compartments. In addition, the panel provided readouts of T cell and NK cell function that correlated with ICI efficacy and with increases in tumor cytokines, including IFNγ, CXCL10, and CCL5, without the need for lengthy ex vivo stimulation and intracellular cytokine staining. The use of autofluorescence extraction and the designation of autofluorescence tags, which is possible on spectral flow cytometers, was essential to properly identify populations. We demonstrate the ability of modern spectral flow cytometers to produce remarkably consistent data over time, without the need for manual detector gain adjustments, which could improve data interpretation between investigators and facilitate the development of novel therapies. Citation Format: Joseph P. Kolb, Kathryn R. Meshaw, Timothy Hutchinson, Karsten Fynboe, Jacob Hauser, William D. Culp, Beth A. Hollister. A spectral flow cytometry panel and workflow for the reproducible assessment of colorectral tumor immunophenotype in the context of immunotherapies [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 2189.
Abstract 1221: Modelling the heterogeneity of high grade serous ovarian tumors in 3D to study its metabolic response to atovaquone
Authors: Paula M. Manan-Mejias, Nicha Boonpattrawong, Manish Patankar, Maria Virumbrales Munoz
Journal: Cancer Research (2025)

Ovarian cancers are the 8th most common cause of cancer related deaths in women, which outcomes have not meaningfully improved since the 1980s. High-grade serous ovarian carcinoma (HGSOC), is the most common subtype of ovarian cancer and the deadliest, responsible for 70-80% of ovarian cancer deaths. HGSOC is typically diagnosed at advanced stages, due to lack of reliable tests and vague external symptoms. When detected, treatment options are limited and result in a 60% recurrence rate. Consequently, there is an urgent need for new therapeutic agents for HGSOC. Atovaquone is an FDA-approved drug for malaria that has been effective against HGSOC in 2D models. Atovaquone (ATO) is an OXPHOS inhibitor that induces reactive oxygen species (ROS) by binding to complex III, leading to apoptosis. However, the mechanism of action of Atovaquone is not well understood, arguably limited to using traditional HGSOC models in mechanistic studies. For example, 2D in-vitro models fail to include oxygen and nutrient gradients, as well as relevant mitochondrial organization for 3D migration processes, whereas in-vivo models make real-time cell inspection challenging. To bridge this gap, we have designed a microphysiological system (MPS) to investigate the role of the 3D tumor microenvironment (TME) in the HGSOC response to therapeutics. Our MPS includes an HGSOC cell spheroid that models intra-tumor metabolic heterogeneity, by recapitulating a necrotic core, quiescent area, and proliferative edge. Adjacent to the tumor spheroid, we can include 3D tubular vessels to study the delivery and effects of atovaquone in lymphatic drainage. Migration and invasion of HGSOC spheroids decrease with ATO treatment. We also showed that atovaquone alters mitochondrial dynamics within 48-72 h of treatment. In addition, a non-destructive imaging technique capable of assessing real-time metabolic profiles in spheroids, revealed that ATO is capable of shifting cancer cell metabolism in spheroids, impeding ATP production. Using this HGSOC MPS, we aim to better understand the mechanism of action of atovaquone and accelerate its translation into the clinic as a sole or combination therapy agent. Citation Format: Paula M. Manan-Mejias, Nicha Boonpattrawong, Manish Patankar, Maria Virumbrales Munoz. Modelling the heterogeneity of high grade serous ovarian tumors in 3D to study its metabolic response to atovaquone [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 1221.
Abstract 1279: Preclinical syngeneic model and xenograft model for evaluating CD3/HER2 bispecific antibody therapy
Authors: Fengqian Chen, Chong Li, Qinjun Wang, Qiang Liu, Baihong Liu, Jiansu Zhang, Xiaofei Zhou
Journal: Cancer Research (2025)

Abstract Abnormal expression of HER2 in normal cells and tissues makes them susceptible to carcinogenesis, leading to tumor formation. HER2 gene amplification or protein overexpression has been found in various human tumors, including breast cancer, gastric cancer, and ovarian cancer. The approval of multiple anti-HER2 drugs has greatly improved the prognosis for patients with HER2-positive solid tumors. However, in clinical practice, some HER2-positive patients have developed resistance, possibly due to an immunosuppressive tumor microenvironment (TME). The CD3/HER2 bispecific antibody (BsAb) is considered a strategy to overcome this immunosuppressive TME by redirecting T cells to HER2-expressing tumor cells, thereby killing HER2-positive tumor cells. Biocytogen developed a BsAb Ab1 that targets human CD3 and human HER2, and evaluated its efficacy and mechanism of action in preclinical studies. In vitro cytotoxicity assays showed that CD3/HER2 BsAb Ab1 significantly induced T cell activation and exhibited effective killing effects against B-hHER2 MC38 plus cell line expressing human HER2. In a syngeneic transplantation model using B-hCD3E/hHER2 mice inoculated with the B-hHER2 MC38 plus cell line, BsAb Ab1 effectively inhibited tumor growth. Additionally, CD3/HER2 BsAb also significantly inhibited the growth of human tumor cells NCI-N87 in a PBMC reconstitution model using B-NDG mice. These results indicate that both models are suitable for the preclinical evaluation of the CD3/HER2 BsAb. Citation Format: Fengqian Chen, Chong Li, Qinjun Wang, Qiang Liu, Baihong Liu, Jiansu Zhang, Xiaofei Zhou. Preclinical syngeneic model and xenograft model for evaluating CD3/HER2 bispecific antibody 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 1279.
Abstract 772: Spatial analysis of the DLBCL tumor microenvironment via the novel SignalStarTM multiplex immunohistochemistry assay
Authors: Jennifer Ziello, Shuling Zhang, Derek Papalegis, Lily Vu, Gabriella Spang, Jean Loebelenz, Arvin Ruiz, Giorgio Inghirami, Sarah Klein
Journal: Cancer Research (2025)

Abstract Diffuse Large B-Cell Lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, accounting for more than 18, 000 cases each year within the United States. While roughly 60% of patients with DLBCL achieve durable remissions with existing chemotherapies, the prognosis of patients with refractory DLBCL is poor. The immune landscape of DLBCL is complex and further elucidation of the interplay between T cell activation and immunosuppression within the tumor microenvironment (TME) is necessary in order to better stratify patients and predict outcomes for therapy. This complexity, as well as the relevance of the spatial context of the various cell types within the TME necessitate the ability to simultaneously visualize biomarkers and phenotypic markers via multiplex immunohistochemical (mIHC) assays. Here, we construct a 12-plex SignalStar mIHC panel consisting of T cell phenotypic, activation and suppression markers in order to characterize the TME of FFPE DLBCL cores. We visualize immuno-oncology markers in the context of the tumor and myeloid cells, as defined by CD68. In this assay, all 12 antibodies are applied in one primary incubation, followed by the addition of a network of fluorescently-labeled oligonucleotides used to amplify the signal of 4 antibody-oligo conjugates across 3 rounds of imaging. Following amplification and imaging of the first 4 conjugates, the fluorescent signal was enzymatically removed and the process repeated for two more rounds. The three resulting images were then aligned using Visiopharm’s TissuealignTM platoform. Quantitative analysis, including positive cell counts and marker co-localization, was conducted with Visiopharm’s PhenoplexTM. Biomarker expression patterns were also examined using PhenoplexTM. Finally, we correlated these data with patient demographics, disease progression, and treatment responses. Our data demonstrate that the SignalStar mIHC assay is a powerful tool in the elucidation of the complex immunosuppressive TME, enabling researchers to better understand the responses to immunotherapeutic approaches and chemotherapy combination strategies. Citation Format: Jennifer Ziello, Shuling Zhang, Derek Papalegis, Lily Vu, Gabriella Spang, Jean Loebelenz, Arvin Ruiz, Giorgio Inghirami, Sarah Klein. Spatial analysis of the DLBCL tumor microenvironment via the novel SignalStarTM multiplex immunohistochemistry assay [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 772.
Abstract 345: Trop2 and B7H4 bi-specific ADC with improved efficacy and safety for gynecologic cancers
Authors: Jing Chen, Chenjuan Zhu, Chenchen Zhu, Zhongmin Liu, Min Wu, Weiwei Wu, Junjie Deng, Yi Wang, Xiguang Zhang, Yiming Li
Journal: Cancer Research (2025)

Abstract The effectiveness of Antibody-Drug Conjugates (ADCs) is closely associated with the level of tumor antigen expression and the administered drug dose, as observed in both preclinical and clinical settings. Trop2-targeted ADCs represent a promising therapeutic approach for various solid tumors; however, their efficacy is constrained by the expression levels of Trop2 and the off-tumor, on-target toxicity. To address these limitations, we have developed a bi-specific ADC that targets both Trop2 and B7H4, aiming to increase the overall tumor antigen expression level, and reduce the off-tumor toxicity associated with Trop2 by incorporating a single-arm Trop2 antibody and employing a less toxic Topoi NT3 linker payload in the ADC. Our research has confirmed the co-expression of Trop2 and B7H4 on tumor cells in Triple Negative Breast Cancer, ovarian cancer, and endometrial cancer, while not on normal mucosal epithelial cells. This co-expression profile supports the use of our bi-specific approach to improve cancer targeting efficiency while minimizing toxicity to normal tissues. In vitro studies demonstrate that our bi-specific Trop2/B7H4 ADC (IBI3022) exhibits superior cytotoxicity in HT29 cells overexpressing Trop2 and B7H4 compared to mono-specific ADC benchmarks targeting Trop2 or B7H4. Additionally, IBI3022 shows comparable efficacy to B7H4 ADC in B7H4-positive HCC1569 cells and to Trop2 ADC IBI130 in Trop2-positive BxPC3 and HCC1954 cells. In vivo, IBI3022 demonstrates enhanced tumor suppression compared to mono-specific ADC benchmarks in various tumor models with differing levels of Trop2 and B7H4 expression, including MDA-MB-468, HT29-Trop2-B7H4, HCC1806, JIMT1, and NUGC4. The half-life of IBI3022 in mice is 113 hours, supporting its sustained in vivo efficacy. The developability profile of IBI3022 is favorable, and notably, it is well-tolerated in cynomolgus macaques at doses up to 50 mg/kg. Overall, IBI3022 represents a promising bi-specific ADC for the treatment of gynecologic cancers, offering improved efficacy and safety profiles. Citation Format: Jing Chen, Chenjuan Zhu, Chenchen Zhu, Zhongmin Liu, Min Wu, Weiwei Wu, Junjie Deng, Yi Wang, Xiguang Zhang, Yiming Li. Trop2 and B7H4 bi-specific ADC with improved efficacy and safety for gynecologic cancers [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 345.