tbuckley/cabot-search huggingface dataset:
68Ga DOTATATE PET/MR Imaging of Well-Differentiated Primary and Metastatic Liver Neuroendocrine Tumors
Authors: Cigdem Soydal, Burak Demir, Pinar Akkus Gunduz, Muhammet Halil Baltacioglu, Mine Araz, Digdem Kuru Oz, Nuriye Ozlem Kucuk
Journal: Clinical Nuclear Medicine (2025)

Purpose: To evaluate the potential of integrated multiparametric 68 Ga DOTATATE PET/MR imaging for assessing liver lesions of well-differentiated neuroendocrine tumors (NETs) and to identify imaging parameters predictive of primary tumor localization. Patients and Methods: This retrospective study involves patients with well-differentiated NETs who underwent 68 Ga DOTATATE PET/MRI between September 2018 and November 2024. Inclusion criteria required histopathologically proven NETs with 68 Ga DOTATATE-avid liver metastases and complete multiparametric MRI sequences. PET and MRI-derived variables, including SUV max , ADC min , T/L ratios, and tumor volume (log-transformed tumor volume: LOGVOL), were analyzed. Linear mixed-effects models and logistic regression analyses were performed to identify relationships between imaging features and tumor characteristics. ROC analyses were conducted to evaluate the accuracy of primary tumor origin predictions. Results: Of 43 imaging sessions, 14 patients (7 male, 7 female; median age 59 y) with 181 lesions met the inclusion criteria. SUV max was significantly correlated with LOGVOL and contrast enhancement parameters (eg, WO liver ). Linear mixed-effects models revealed that LOGVOL and WO liver were independent predictors of SUV max . In the binomial regression analysis, tumor precontrast T1 intensity, T/L art , and T/L ven were significant factors in differentiation between pancreatic and gastrointestinal (GIS) NET metastases, with pancreatic tumors demonstrating higher T/L art and GIS tumors exhibiting higher T/L ven and T1 intensity. Logistic regression achieved an AUC of 0.911, with a sensitivity of 86% and specificity of 76%. Conclusion: 68 Ga DOTATATE PET/MRI effectively integrates metabolic and anatomical imaging for characterizing NET liver metastases. Parameters such as LOGVOL and WO liver independently predict SUV max , while precontrast T1 intensity, T/L art , and T/L ven assist in differentiating pancreatic from GIS NETs. These findings underscore the potential of 68 Ga DOTATATE PET/MRI in personalized NET management and suggest avenues for further research to confirm these results.
Intracranial and Extracranial Vascular Involvement in Takayasu Arteritis Unresponsive to Multiple Lines of Immunomodulation on 68Ga-FAPI PET/CT
Authors: Srinivas Ananth Kumar, Madhur Kumar Srivastava, Kambhampatti Sree lekha, Challa Madhuri, Phani Kumar
Journal: Clinical Nuclear Medicine (2025)

Takayasu arteritis (TAK) is a large-vessel vasculitis characterized by granulomatous inflammation of the aorta and its primary branches. The clinical presentation of TAK is heterogeneous. Intracranial vascular involvement in TAK is uncommon and is understudied. Clinical, biochemical, and imaging data always do not correspond, making it difficult to evaluate disease activity in TAK. FAPI PET/CT is a noninvasive whole-body imaging modality that could potentially aid in diagnosis, therapy monitoring, and identifying disease relapse when 18 F-FDG-PET/CT is inconclusive. The authors in this research demonstrate intracranial and extracranial vascular involvement in a patient of TAK on 68 Ga-FAPI-04 PET/CT.
Early-Stage Mycosis Fungoides: Searching for biomarkers associated with advanced stage progression
Authors: Marcos Rebollo-González, Vanessa Gargallo-Moneva, Alicia Sánchez-Martínez, Juan Torre-Castro, Carmen Herencia, María Moreno-Delgado, Ruth Alonso-Alonso, Rebeca Manso, Jennifer Borregón, Francisco Javier Díaz de la Pinta, Raquel Pajares, Alfonso Gotor-Rivera, Ignacio Torres-Navarro, Daniel Morillo-Giles, Carlos Moreno-Vílchez, Daniel Martín-Torregrosa, Cristina Muniesa, Octavio Servitje, Fina Climent, Jesús Frutos Díaz-Alejo, Raquel Rivera-Díaz, Pablo Luis Ortiz-Romero, José Luis Rodríguez-Peralto, Socorro María Rodríguez-Pinilla, Marta Rodríguez
Journal: British Journal of Dermatology (2025)

This study shows that the microenvironment and probably the phenotype of neoplastic T-cells of early-stage MF samples from MF-patients who suffered progression or remained stable is different. Moreover, we propose that the overexpression of CD30, CXCL13 and BIRC3 in early-stage MF is related to progression. Further spatial transcriptomics studies or single cell analysis in further series of cases are needed to corroborate our findings.
Intrinsic immunogenicity is a major determinant of type-specific responses in SARS-CoV-2 infections
Authors: Grace E Quirk, Marta V Schoenle, Kameron L Peyton, Jennifer L Uhrlaub, Branden Lau, Chieh-Yu Liang, Jefferey L Burgess, Katherine Ellingson, Shawn Beitel, James Romine, Karen Lutrick, Ashley Fowlkes, Amadea Britton, Harmony L Tyner, Alberto J Caban-Martinez, Allison Naleway, Manjusha Gaglani, Sarang Yoon, Laura J Edwards, Lauren Olsho, Michael Dake, Riccardo Valdez, Aubree Gordon, Michael S Diamond, Bonnie J LaFleur, Janko Ž Nikolich, Ryan Sprissler, Michael Worobey, Deepta Bhattacharya
Journal: Nature Immunology (2025)
Randomized Phase II Study of Concurrent Versus Sequential Pembrolizumab in Combination With Chemoradiation in Locally Advanced Head and Neck Cancer
Authors: Dan P. Zandberg, Lazar Vujanovic, David A. Clump, Brian P. Isett, Hong Wang, Gabriel Sica, Riyue Bao, Housayin Li, James Ohr, Heath D. Skinner, Raja R. Seethala, Simion I. Chiosea, Robert L. Ferris, Julie E. Bauman
Journal: Journal of Clinical Oncology (2025)

PURPOSE The optimal timing of pembrolizumab with chemoradiation (CRT) in locally advanced (LA) head and neck squamous cell carcinoma (HNSCC) is unknown. Patients and Methods Our phase II trial randomly assigned patients 1:1 to concurrent pembrolizumab (200 mg once every 3 weeks × 8) starting 1 week before CRT (cisplatin 40 mg/m 2 once weekly + radiation 70 Gy) versus sequential pembrolizumab starting 2 weeks after CRT. Human papillomavirus (HPV)+ (&gt;10 pack-years or T4 or N3) and HPV(–) LA HNSCC were included, stratified by HPV and N stage. In our pick-the-winner design, if both arms met the trivariate primary end point (1-year locoregional failure &lt;60%, progression-free survival [PFS] ≥60%, and dose limiting toxicity rate ≤20%), the arm with numerically superior 1-year PFS would be selected. Survival end points were compared by a univariate Cox model. Pretreatment and on-treatment tumor biopsies (week 2 of CRT) were evaluated by multispectral imaging and compared using two-sided paired t -tests. RESULTS Treated patients (41 concurrent and 39 sequential) were 71% oropharynx (53% HPV+), 92.5% stage IV (46% T4, 76% N2), similar by arm. Both arms met the trivariate primary end point, with superior 1-year PFS in the sequential arm (84% v 71%) and favorable 4-year outcomes: locoregional control (96% v 64%; hazard ratio [HR], 0.11 [95% CI, 0.01 to 0.89]; P = .012), PFS (69% v 49%; HR, 0.55 [95% CI, 0.25 to 1.22]; P = .132), and overall survival (83% v 71%; HR, 0.51 [95% CI, 0.19 to 1.37]; P = .17). There was a significant increase in macrophages, PD-L1+ macrophages, and PD-L1+ tumor cells with treatment in the concurrent but not the sequential arm. CONCLUSION CRT with sequential pembrolizumab met criteria for further study. Immunosuppressive changes in the TME differed between arms, reflecting the impact of one dose of pembrolizumab in the concurrent arm.
Magnetic Resonance Imaging–led Risk-adapted Active Surveillance for Prostate Cancer: Updated Results from a Large Cohort Study
Authors: Cameron Englman, Busola Adebusoye, Davide Maffei, Vasilis Stavrinides, Joshua Bridge, Alex Kirkham, Clare Allen, Louise Dickinson, Doug Pendse, Shonit Punwani, Navin Ramachandran, Chun Wah So, Aiman Haider, Alex Freeman, Alistair Grey, Clement Orczyk, John Withington, Karen Wilkinson, Veeru Kasivisvanathan, Mark Emberton, Sue Mallett, Francesco Giganti, Caroline M. Moore
Journal: European Urology (2025)
A distributional reinforcement learning model for optimal glucose control after cardiac surgery
Authors: Jacob M Desman, Zhang-Wei Hong, Moein Sabounchi, Ashwin S Sawant, Jaskirat Gill, Ana C Costa, Gagan Kumar, Rajeev Sharma, Arpeta Gupta, Paul McCarthy, Veena Nandwani, Doug Powell, Alexandra Carideo, Donnie Goodwin, Sanam Ahmed, Umesh Gidwani, Matthew A Levin, Robin Varghese, Farzan Filsoufi, Robert Freeman, Avniel Shetreat-Klein, Alexander W Charney, Ira Hofer, Lili Chan, David Reich, Patricia Kovatch, Roopa Kohli-Seth, Monica Kraft, Pulkit Agrawal, John A Kellum, Girish N Nadkarni, Ankit Sakhuja
Journal: npj Digital Medicine (2025)
A highly selective and orally bioavailable casein kinase 1 alpha degrader through p53 signaling pathway targets B-cell lymphoma cells
Authors: Shi Feng, Ran Kong, Cong Wang, Qingbo Hao, Xiaoyu Xie, Haiyang Wang, Jingjing Han, Yu Zhang, Jan Elsner, Derek Mendy, Michael Haughey, Paul Krenitsky, Veronique Plantevin-Krenitsky, Patrick Papa, Frank Mercurio, Weilin Xie, Xiangxiang Zhou
Journal: Leukemia (2025)
Risk of aggressive prostate cancer with successive generations in the U.S. among Latino men
Authors: Fei Chen, Adelynn Paik, Xin Sheng, Iona Cheng, Salma Shariff-Marco, Lynne R Wilkens, Loïc Le Marchand, David V Conti, Christopher A Haiman, Veronica Wendy Setiawan
Journal: JNCI Journal of the National Cancer Institute (2025)

Abstract Background US-born Latino men have a higher incidence of prostate cancer (PCa) than foreign-born Latino men. It was not clear whether these increases were exclusively due to increased detection of PCa in the US, changes in risk factors of PCa, or a combination of both. Methods In the Multiethnic Cohort (MEC) we evaluated the association between generational status and risk of PCa in 19,597 Latino men, adjusting for demographic and lifestyle factors, individual- and neighborhood-level socioeconomic status (SES), as well as history of PSA screening. Additional adjustments on polygenic risk score (PRS) and genetic ancestry were included in the sensitivity analysis in the biorepository cohort with genetic data. Results This analysis included 10,241 1st-generation, 4,610 2nd-generation, and 4,746 3rd-generation Latino men, among whom 2,366 PCa were diagnosed during an average of 19.2 years of follow-up. After adjusting for covariates, we observed no association between generational status and risk of overall, localized, or low-grade PCa. A per generation increase was significantly associated with a 13% to 15% elevated risk of high-grade, advanced, or aggressive PCa. These associations with aggressive forms of PCa remained significant in the biorepository cohort with additional adjustment on PRS and genetic ancestry. Conclusions Successive generations in the US were associated with an increased risk of aggressive forms of PCa among Latino men and the observed increases cannot be explained by differences in genetic susceptibility, ancestry, PSA screening, lifestyle, and SES factors. Further investigations are needed to identify additional factors that contribute to this increased risk.
Risk of Hematologic Malignancies in Patients With Acute Myocardial Infarction
Authors: Seug Yun Yoon, Mina Kim, Hoseob Kim, Duk Won Bang, Byoung-Won Park, Sun Young Jeong, Min-Young Lee, Kyoung Ha Kim, Namsu Lee, Jong-Ho Won, Inki Moon, Jon Suh, Seong Soon Kwon
Journal: JACC CardioOncology (2025)

Acute myocardial infarction (AMI) and cancer are leading causes of death worldwide. However, the relationship between AMI and hematologic malignancies remains unclear. The authors aimed to investigate the association between AMI and the subsequent risk of incident hematologic malignancies. This retrospective cohort study included 103,686 patients with AMI and no history of hematologic malignancies, and 103,686 age- and sex-matched individuals with no history of AMI or hematologic malignancies, diagnosed between January 1, 2003, and December 31, 2021. Data were obtained from the Korean National Health Insurance claims database. We compared the cumulative incidence of hematologic malignancies between groups using Gray's method. HRs and 95% CIs were calculated using Gray's competing risk regression model, with death treated as a competing risk. During follow-up (AMI, 7.9 years [Q1-Q3: 5.2-11.4 years]; control group, 17.8 years [Q1-Q3: 14.8-17.9 years]), 1,043 and 1,479 individuals in the AMI and control groups, respectively, were newly diagnosed with hematologic malignancies (incidence rate per 1,000 person-years: 1.21 vs 0.93). Competing risk analysis revealed that the AMI group had a higher risk of hematologic malignancy than the control group (HR: 1.49; 95% CI: 1.31-1.69). Findings were consistent in sensitivity and standardized incidence ratio analyses. Patients with AMI had a higher risk of hematologic malignancies than those without AMI. These findings suggest an association between AMI and hematologic malignancies, and underscore the importance of considering hematologic malignancy development in patients with AMI.
Albuminuria as a diagnostic criterion and a therapeutic target in heart failure and other cardiovascular disease
Authors: Biykem Bozkurt, Patrick Rossignol, Joseph A. Vassalotti
Journal: European Journal of Heart Failure (2025)

Abstract The high disease burden and bidirectional relationship of chronic kidney disease (CKD), heart failure (HF) and other cardiovascular disease (CVD) necessitate the need for early diagnosis of these diseases. While current screening and detection methods are recommended by CKD and CVD guidelines, their adoption in practice is low. Urine albumin‐to‐creatinine ratio (uACR) is recognized as a diagnostic marker for CKD and a prognostic marker for CKD progression, HF and CVD outcomes, therefore albuminuria changes have been accepted as a surrogate outcome for kidney and cardiovascular endpoints. Furthermore, clinical trials investigating guideline‐directed medical therapies have shown that uACR reductions are accompanied by risk reductions for cardiovascular, HF and other CKD outcomes. However, uACR is not routinely measured in patients at risk of kidney and heart disease, and its utility for detection, risk stratification and prediction models may not be fully appreciated in routine clinical practice. This review will discuss the effectiveness and implications of uACR screening as a method for heart and kidney disease diagnosis and risk assessment.
Chemical knockdown of Keap1 and homoPROTAC-ing allergic rhinitis
Authors: Jianyu Yan, Tianyu Wang, Ruizhi Yu, Lijuan Xu, Hongming Shao, Tengfei Li, Zhe Wang, Xudong Cha, Zhenyuan Miao, Chengguo Xing, Ke Xu, Huanhai Liu, Chunlin Zhuang
Journal: Acta Pharmaceutica Sinica B (2025)
Quantifying diagnostic intervals and routes to diagnosis for children and young people with cancer in the UK (Childhood Cancer Diagnosis study, CCD): a population-based observational study
Authors: Dhurgshaarna Shanmugavadivel, Jo-Fen Liu, Timothy A. Ritzmann, Ashley Ball-Gamble, Angela Polanco, Neil Ranasinghe, Kavita Vedhara, Shalini Ojha, David Walker
Journal: The Lancet Regional Health - Europe (2025)
Disease Modifying, Multidimensional Efficacy of Putaminal CaV1.3-shRNA Gene Therapy in Aged Parkinsonism Male and Female Macaques
Authors: Kathy Steece-Collier, Margaret E. Caulfield, Molly J. Vander Werp, Scott J. Muller, Jennifer A. Stancati, Yaping Chu, Ivette M. Sandoval, Timothy J. Collier, Jeffrey H. Kordower, Fredric P. Manfredsson
Journal: Molecular Therapy (2025)
Modeling breast cancer dynamics through modulable small Vessel Environment Bioreactor (sVEB)
Authors: Fabio Maiullari, Maria Grazia Ceraolo, Dario Presutti, Nicole Fratini, Matteo Galbiati, Alessandra Fasciani, Konrad Giżyński, Salma Bousselmi, Francesca Megiorni, Cinzia Marchese, Piotr Kasprzycki, Karol Karnowski, Alessandro Talone, Gaspare Varvaro, Davide Peddis, Marco Costantini, Claudia Bearzi, Roberto Rizzi
Journal: Biomaterials (2025)
Association of state-level PrEP coverage and new HIV diagnoses in the USA from 2012 to 2022: an ecological analysis of the population impact of PrEP
Authors: Patrick S Sullivan, Marta Juhasz, Stephanie N DuBose, Gordon Le, Kamaria Brisco, Duygu Islek, James Curran, Eli Rosenberg
Journal: The Lancet HIV (2025)
Incidence, microbiology and mortality of ventilation-associated pneumonia in a large Italian cohort of critically ill patients. Results from the PROSAFE project
Authors: Marta Colaneri, Giorgia Montrucchio, Giovanni Scaglione, Gianpaola Monti, Giovanni Tricella, Camilla Genovese, Fulvio Agostini, Francesca Dore, Bruno Viaggi, Luca Brazzi, Valentina Sanna, Andrea Gori, Emanuele Palomba, Martina Offer, Stefano Finazzi, Giorgia Montrucchio, Fulvio Agostini, Antonello di Paolo, Angelo Pan, Carla Maria Zotti, Costanza Vicentini, Bruno Viaggi, Gianpaola Monti, Gian Maria Rossolini, Daniela Silengo, Emanuele Russo, Lidia Dalfino, Marta Colaneri
Journal: Clinical Microbiology and Infection (2025)
Enhanced Cerenkov radiation induced photodynamic therapy based on GSH-responsive biomimetic nanoplatform to trigger immunogenic cell death for tumor immunotherapy
Authors: Ruijie Qian, Yawen Guo, Xuemei Gao, Jianzhuang Ren, Dawei Jiang, Rui An, Ruihua Wang, Xuhua Duan, Xinwei Han
Journal: Asian Journal of Pharmaceutical Sciences (2025)
The epidemiology and burden of injury in countries of the Association of Southeast Asian Nations (ASEAN), 1990–2021: findings from the Global Burden of Disease Study 2021
Authors: Stephanie C C van der Lubbe, Lin Siew Chong, Simon I Hay, Catherine Bisignano, Spencer L James, Xiaochen Dai, Lay Hoon Goh, Swetha Acharya, Qorinah Estiningtyas Sakilah Adnani, Naveed Ahmed, Budi Aji, Joseph Uy Almazan, Carl Abelardo T Antonio, Sumadi Lukman Anwar, Muhammad Shahzad Aslam, Atif Amin Baig, Amiel Nazer C Bermudez, Ahmad Naoras Naoras Bitar, Muthia Cenderadewi, Hana Chen, Nicholas WS Chew, Bryan Chong, Mayank Dalakoti, Hisham Atan Edinur, Crystal Amiel M Estrada, Emerito Jose Aquino Faraon, Nelsensius Klau Fauk, Ida Fitriana, Ni Kadek Yuni Fridayani, Fernando Barroga Garcia, Arief Hargono, Eka Mishbahatul Marah Has, Paul Michael Rafa Hernandez, Nahlah Elkudssiah Ismail, Vikash Jaiswal, Roland Dominic G Jamora, Jost B Jonas, Kehinde Kazeem Kanmodi, Inn Kynn Khaing, Yun Jin Kim, Chong-Han Kua, Maria Dyah Kurniasari, Asep Kusnali, Dian Kusuma, Hilton Lam, Shaun Wen Huey Lee, Zheng Feei Ma, Roy Rillera Marzo, Kamarul Imran Musa, Firzan Nainu, Dina Nur Anggraini Ningrum, Sok King Ong, Veincent Christian Filipino Pepito, Thantrira Porntaveetus, Dimas Ria Angga Pribadi, Sheena Ramazanu, Bedanta Roy, Yoseph Leonardo Samodra, Siddharthan Selvaraj, Shazlin Shaharudin, Robert Sinto, Solikhah Solikhah, Chandrashekhar T Sreeramareddy, Vetriselvan Subramaniyan, Thitiporn Sukaew, Ingan Ukur Tarigan, Jansje Henny Vera Ticoalu, Narayanaswamy Venketasubramanian, Taweewat Wiangkham, Anggi Lukman Wicaksana, Siyan Yi, Mustafa Z Younis, Christopher J L Murray, Kanyin Liane Ong, Yee Wei Lim, Marie Ng
Journal: The Lancet Public Health (2025)
Effects of hearing intervention on falls in older adults: findings from a secondary analysis of the ACHIEVE randomised controlled trial
Authors: Adele M Goman, Nasya Tan, James Russell Pike, Sarah Y Bessen, Ziheng (Sally) Chen, Alison R Huang, Michelle L Arnold, Sheila Burgard, Theresa H Chisolm, David Couper, Jennifer A Deal, Nancy W Glynn, Theresa Gmelin, Lisa Gravens-Mueller, Kathleen M Hayden, Pablo Martinez-Amezcua, Christine M Mitchell, James S Pankow, Nicholas S Reed, Victoria A Sanchez, Jennifer A Schrack, Kevin J Sullivan, Josef Coresh, Frank R Lin
Journal: The Lancet Public Health (2025)
The epidemiology and burden of smoking in countries of the Association of Southeast Asian Nations (ASEAN), 1990–2021: findings from the Global Burden of Disease Study 2021
Authors: Xiaochen Dai, Marie Ng, Gabriela Fernanda Gil, Brooks W Morgan, Jason A Anderson, Qorinah Estiningtyas Sakilah Adnani, Budi Aji, Syed Mohamed Aljunid, Gianna Gayle Herrera Amul, Sumadi Lukman Anwar, Geminn Louis Carace Apostol, Kurnia Dwi Artanti, Sarunya Benjakul, Amiel Nazer C Bermudez, Bryan Chong, Dinh-Toi Chu, Thanh Chi Do, Ferry Efendi, Diyan Ermawan Effendi, Nelsensius Klau Fauk, Arief Hargono, Eka Mishbahatul Marah Has, Hong-Han Huynh, Endang Indriasih, Muhammad Iqhrammullah, Ammar Abdulrahman Jairoun, Kehinde Kazeem Kanmodi, Helda Khusun, Maria Dyah Kurniasari, Dian Kusuma, Tri Laksono, Nhi Huu Hanh Le, Thao Thi Thu Le, Stefan Ma, Roy Rillera Marzo, Mustapha Mohammed, Christopher J L Murray, Gustavo G Nascimento, Phat Tuan Nguyen, Van Thanh Nguyen, Dina Nur Anggraini Ningrum, Efaq Ali Noman, Erin M O'Connell, Sok King Ong, Bedanta Roy, Sher Zaman Safi, Made Ary Sarasmita, Siddharthan Selvaraj, Sunil Shrestha, Solikhah Solikhah, Chandrashekhar T Sreeramareddy, Yen Lian Tan, Ingan Ukur Tarigan, Jansje Henny Vera Ticoalu, Thien Tan Tri Tai Truyen, Narayanaswamy Venketasubramanian, Maniphanh Vongphosy, Tati Suryati Suryati Warouw, Angga Wilandika, Siti Rosemawati Yussof, Simon I Hay, Emmanuela Gakidou
Journal: The Lancet Public Health (2025)
Blood Pressure Lowering Effects of a Novel Long-Acting NPR1 Agonist, XXB750, in Healthy Participants: A Randomized, First-in-Human Clinical Study
Authors: YanLing He, Xueping Wu, Andre Serra-Roma, Maggie Markiewicz, Emma Healy, Jing-He Yan, Kenneth Kulmatycki, Tong Zhang, John L. Diener, Arvind G. Kinhikar, Denise P. Yates, David Nguyen, Markus Hinder, Cesare Russo, Christopher J. O’Donnell
Journal: Circulation (2025)
Response by Kristensen et al to Letter Regarding Article, “Half-Life and Clearance of Cardiac Troponin I and Troponin T in Humans”
Authors: Jonas Henrik Kristensen, Rasmus Bo Hasselbalch, Nina Strandkjær, Peter Hasse Møller-Sørensen, Pia Rørbæk Kamstrup, Morten Dahl, Mustafa Vakur Bor, Ruth Frikke-Schmidt, Niklas Rye Jørgensen, Line Rode, Lene Holmvang, Jesper Kjærgaard, Lia Evi Bang, Julie Forman, Kim Dalhoff, Allan S. Jaffe, Kristian Thygesen, Henning Bundgaard, Kasper Karmark Iversen
Journal: Circulation (2025)
Development of an Anti-CD99 Antibody Enables Targeting of Diffuse Midline Glioma
Authors: Ilango Balakrishnan, Krishna Madhavan, Angela Pierce, Joshua Michlin, Breauna Brunt, Senthilnath Lakshmanachetty, Dong Wang, John DeSisto, Zachary James. Nuss, Nathan Davidson, Faye Walker, Ammu Suresh, Andrew Donson, Bridget Sanford, Kenneth L. Jones, Etienne P. Danis, Siddhartha S. Mitra, Adam L. Green, Nathan Dahl, Rajeev Vibhakar, Sujatha Venkataraman
Journal: Cancer Research (2025)

Abstract Diffuse midline gliomas (DMGs) are devastating brain tumors that occur primarily in children. The salient feature of these tumors is the presence of a H3K27M mutation (K27M), associated with the worst prognosis. Development of effective strategies for treating K27M+ DMG is desperately needed to help improve patient outcomes. Here, we identified the cell surface antigen CD99 as notably expressed in DMGs, particularly in K27M+ DMGs. The increased expression of CD99 in K27M+ DMGs was a result of the onco-histone K27M mutation. In K27M+ DMG cells, CD99 inactivation impaired tumor growth by inducing cell differentiation. The development of a therapeutic anti-CD99 chimeric antibody, 10D1, with a membrane-proximal binding epitope enabled the evaluation of the antitumor efficacy of targeting CD99 in preclinical models of K27M+ DMG. 10D1 suppressed DMG growth in vitro and in vivo by inducing apoptosis. When combined with radiation treatment, 10D1 exhibited improved antitumor efficacy and prolonged xenograft survival. Together, these findings provide a strong justification for the clinical development of 10D1 as a therapy for targeting CD99 to treat DMGs.