Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Despite the revolution of immunotherapy in cancer treatment, patients eventually progress due to the emergence of resistance. In this scenario, the selection of the tumor antigen can be decisive in the success of the clinical response. T cell bispecific antibodies (TCBs) are engineered molecules that include binding sites to the T cell receptor and to a tumor antigen. Using gastric CEA/HER2 MKN45 cells and TCBs directed against CEA or HER2, we show that the mechanism of resistance to a TCB is dependent on the tumor antigen. Acquired resistant models to a high-affinity-CEA-targeted TCB exhibit a reduction of CEA levels due to transcriptional silencing, which is reversible upon 5-AZA treatment. In contrast, a HER2-TCB resistant model maintains HER2 levels and exhibit a disruption of the interferon-gamma signaling. These results will help in the design of combinatorial strategies to increase the efficacy of cancer immunotherapies and to anticipate and overcome resistances.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.celrep.2022.111430 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The effect of CD40 agonist antibody therapy on the pancreatic cancer microenvironment.
Naunyn Schmiedebergs Arch Pharmacol
September 2025
Department of Gastroenterology, Jinhua Central Hospital, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, 321000, Zhejiang, China.
The fourth leading cause of cancer-related fatalities in the USA is pancreatic ductal adenocarcinoma (PDAC), a particularly deadly illness that is resistant to immunotherapy. One of the Main Obstacles in cancer research is developing better treatments for PDAC, which has the lowest 5-year survival rate of any malignancy. Anti-CTLA-4, anti-PD-L1, and anti-PD-1 immune checkpoint blockade medications also have poor results in these patients, which may indicate the presence of other immunosuppressive mechanisms in the pancreatic tumor microenvironment (TME).
View Article and Find Full Text PDFATOR-4066, a bispecific antibody targeting CD40 and CEACAM5, induces strong myeloid and T cell-dependent tumor immunity and synergizes with PD-1 blockade.
Cancer Immunol Res
September 2025
Alligator Bioscience (Sweden), Lund, Sweden.
Despite recent progress within the field of immuno-oncology, immune suppression in the tumor microenvironment, defective antigen presentation, and low levels of tumor-specific T cells are key limitations of current cancer immunotherapies. CD40-targeting immunotherapies hold promises for addressing these limitations across solid tumors. Here, we describe ATOR-4066, a bispecific antibody that targets CD40 and CEACAM5 developed for immunotherapy of cancer using the Neo-X-Prime platform.
View Article and Find Full Text PDFA Review on Biomarker-Enhanced Machine Learning for Early Diagnosis and Outcome Prediction in Ovarian Cancer Management.
Cancer Med
September 2025
Department of Computer Engineering, Social and Biological Network Analysis Laboratory, University of Kurdistan, Sanandaj, Iran.
Background: Ovarian cancer (OC) remains the most lethal gynecological malignancy, largely due to its late-stage diagnosis and nonspecific early symptoms. Advances in biomarker identification and machine learning offer promising avenues for improving early detection and prognosis. This review evaluates the role of biomarker-driven ML models in enhancing the early detection, risk stratification, and treatment planning of OC.
View Article and Find Full Text PDFCurvilinear Peri-Brainstem Hyperintense Signals as a Marker of Leptomeningeal Metastases in Lung Adenocarcinoma: A Multicenter Retrospective Case Series.
Curr Med Imaging
September 2025
Department of Pharmacy, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
Unlabelled: Leptomeningeal metastasis (LM) is a severe complication of solid malignancies, including lung adenocarcinoma, characterized by poor prognosis and diagnostic challenges. This study assesses whether curvilinear peri-brainstem hyperintense signals on MRI are a characteristic feature of LM in lung adenocarcinoma patients.
Methods: This retrospective study analyzed data from multiple centers, encompassing lung adenocarcinoma patients with peri-brainstem curvilinear hyperintense signals on MRI between January 2016 and March 2022.
Unraveling epigenetic drivers of immune evasion in gliomas: mechanisms and therapeutic implications.
Front Immunol
September 2025
Precision Pharmacy and Drug Development Center, Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
Gliomas are the most common primary malignant tumors of the central nervous system (CNS), and despite progress in molecular diagnostics and targeted therapies, their prognosis remains poor. In recent years, immunotherapy has emerged as a promising treatment modality in cancer therapy. However, the inevitable immune evasion by tumor cells is a key barrier affecting therapeutic efficacy.
View Article and Find Full Text PDF