Article Synopsis
- The study investigates the safety and effectiveness of an experimental treatment called 2141-V11, an anti-CD40 antibody, in patients with metastatic cancer.
- It found that the treatment was well tolerated by patients, with no serious side effects, and resulted in tumor reduction in half of the patients, including complete remission in two cases.
- The therapy appears to enhance immune responses by promoting the formation of specialized immune structures and activating T cells, leading to both localized and systemic antitumor effects.
Video Abstracts
Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
CD40 agonism enhances antitumor immunity but is limited by systemic toxicity and poor efficacy. Here, we present a phase 1 study (NCT04059588) of intratumoral (i.t.) 2141-V11, an Fc-engineered anti-CD40 agonistic antibody with enhanced binding to the inhibitory receptor FcγRIIB. Among 12 metastatic cancer patients, 2141-V11 was well tolerated without dose-limiting toxicities. Six patients experienced tumor reduction, including two complete responses in melanoma and breast cancer. 2141-V11 induced regression in injected and non-injected lesions, correlating with systemic CD8 T cell activation and mature tertiary lymphoid structures (TLSs) in complete responders. In CD40/FcγRs humanized mice bearing orthotopic tumors, i.t. 2141-V11 promoted de novo TLS formation, facilitating i.t. CD8 T cell effector responses independent of lymph node priming. The resulting local immune responses by 2141-V11 mediated abscopal antitumor effects and sustained immune memory. These findings demonstrate that i.t. 2141-V11 is safe and promotes immune-privileged tumor microenvironments that promote systemic and durable antitumor immunity.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12360484 | PMC |
| http://dx.doi.org/10.1016/j.ccell.2025.07.013 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Nuclear glycine decarboxylase suppresses STAT1-dependent MHC-I and promotes cancer immune evasion.
EMBO J
September 2025
Department of Infectious Diseases, Medical Research Institute, Zhongnan Hospital of Wuhan University; Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences; Wuhan University, Wuhan, 430071, China.
Inadequate antigen presentation by MHC-I in tumor microenvironment (TME) is a common immune escape mechanism. Here, we show that glycine decarboxylase (GLDC), a key enzyme in glycine metabolism, functions as an inhibitor of MHC-I expression in EGFR-activated tumor cells to induce immune escape by a mechanism independent of its enzymatic activity. Upon EGFR activation, GLDC is phosphorylated by SRC and subsequently translocated to the nucleus in human NSCLC cells.
View Article and Find Full Text PDFExtracellular vesicles of cancer cells induce FOXP3+ fibroblasts and facilitate tumor invasion via the Wnt3-β-catenin pathway.
Oncogene
September 2025
Department of Molecular Medicine and Biochemistry, Akita University Graduate School of Medicine, Akita, Japan.
Forkhead-box-protein P3 (FOXP3) is a key transcription factor in T regulatory cells (Tregs). However, its expression and significance in non-immune stromal cells in the tumor microenvironment remain unclear. Here, we demonstrated FOXP3 expression in stromal fibroblasts of mouse and human gastrointestinal tumors.
View Article and Find Full Text PDFIntestinal taurine acts as a novel immunometabolic modulator of IBD by degrading redundant mitochondrial RNA.
Cell Mol Immunol
September 2025
Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou, China.
Anti-tumor necrosis factor (TNF) therapy for inflammatory bowel disease (IBD) is hampered by issues of nonresponse and resistance, highlighting the urgent need for alternative or complementary treatments. Our study revealed significant upregulation of taurine in the intestinal tissues of IBD patients, which was inversely related to the severity of the disease. A key discovery was that TNF directly induced taurine synthesis in intestinal epithelial cells and increased the production of angiogenin, a nuclease that degrades mitochondrial RNA, which is known to amplify inflammatory responses.
View Article and Find Full Text PDFNovel role of MKRN2 in regulating tumor growth through host microenvironment and macrophage M1 to M2 switch.
Cancer Lett
September 2025
State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, Tianjian Laboratory of Advanced Biomedical Sciences, Department of Radiology, Department of Clinical Research and Translational Medicine, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou,
The tumor microenvironment (TME) plays a pivotal role in cancer progression, though the molecular regulators governing its immunosuppressive properties remain incompletely characterized. In this study, we identify Makorin-2 (MKRN2) as a novel modulator of TME remodeling through integrated analyses of genetically engineered mouse models and human clinical data. Utilizing MKRN2 knockout mice, we observed significantly accelerated tumor growth compared to wild-type control, which was associated with profound alterations in immune cell composition, especially M2 macrophages.
View Article and Find Full Text PDFFunctionalized hyaluronic acid biomaterials-encouraged cancer immunotherapy through CD44-mediated targeting and cell surface engineering: A review.
Int J Biol Macromol
September 2025
Department of Chemical & Biochemical Engineering, Dongguk University, Seoul, 04620, Republic of Korea. Electronic address:
Modified hyaluronic acid (HA) biomaterials have received considerable attention in recent years, especially in developing innovative therapeutic strategies for targeted disease interventions. HA serves to shield therapeutics from the physiological environment, while enabling safe delivery and promoting uptake into specific cells. As a hydrophilic chain polymer, HA is readily chemically modified into functional biomaterials for drug delivery and cancer immunotherapy.
View Article and Find Full Text PDF