A Phase I, Open-label, Multi-center Study to Evaluate the Safety, Tolerability, Dosimetry and Preliminary Activity of [177Lu]Lu-FF58 in Patients With Selected Advanced Solid Tumors.

The purpose of the study is to test the safety and dosing of [177Lu]Lu-FF58, a radioligand therapy for patients with advanced or metastatic tumors that express proteins known as integrins: alpha-v beta-3 integrin (αvβ3) and alpha-v beta-5 integrin (αvβ5). The study will also further characterize the radioligand imaging agent [68Ga]Ga-FF58 including its ability to identify tumor lesions and its safety profile.

Start Date06 Oct 2023

Sponsor / Collaborator

Novartis Pharmaceuticals Corp.

NL-OMON54735 / RecruitingPhase 2IIT

FLUOPANC-trial - Intraoperative near-infrared fluorescence imaging in pancreatic- and extrahepatic bile duct tumors using cRGD-ZW800-1 and dedicated imaging systems: A phase II feasibility, dose-ranging and optimal dose-(interval) selection trial - FLUOPANC-trial

Start Date24 Nov 2022

Sponsor / Collaborator-

100 Clinical Results associated with αvβ5

100 Translational Medicine associated with αvβ5

0 Patents (Medical) associated with αvβ5

833

Literatures (Medical) associated with αvβ5

31 Dec 2024·mAbs

Synthetic integrin antibodies discovered by yeast display reveal αV subunit pairing preferences with β subunits

Article

Author: Jiang, Aiping ; Lloyd, Kenneth ; Anuganti, Murali ; Yan, Jiabin ; Meijers, Rob ; Li, Jing ; Coppola, Jessica ; Jardine, Joseph ; Zhang, Roushu ; Hao, Yuxin ; Springer, Timothy A ; Fraser, Courtney

Integrins are cell surface receptors that mediate the interactions of cells with their surroundings and play essential roles in cell adhesion, migration, and homeostasis. Eight of the 24 integrins bind to the tripeptide Arg-Gly-Asp (RGD) motif in their extracellular ligands, comprising the RGD-binding integrin subfamily. Despite similarity in recognizing the RGD motif and some redundancy, these integrins can selectively recognize RGD-containing ligands to fulfill specific functions in cellular processes. Antibodies against individual RGD-binding integrins are desirable for investigating their specific functions, and were selected here from a synthetic yeast-displayed Fab library. We discovered 11 antibodies that exhibit high specificity and affinity toward their target integrins, i.e. αVβ3, αVβ5, αVβ6, αVβ8, and α5β1. Of these, six are function-blocking antibodies and contain a ligand-mimetic R(G/L/T)D motif in their CDR3 sequences. We report antibody-binding specificity, kinetics, and binding affinity for purified integrin ectodomains, as well as intact integrins on the cell surface. We further used these antibodies to reveal binding preferences of the αV subunit for its 5 β-subunit partners: β6 = β8 > β3 > β1 = β5.

01 Nov 2024·Cancer Letters

Identification of SPP1+ macrophages in promoting cancer stemness via vitronectin and CCL15 signals crosstalk in liver cancer

Article

Author: Wang, Yizhou ; Xia, Yong ; Li, Haoyu ; Wang, Yue ; Tao, Shuangfen ; Wang, Qing ; Yang, Cheng ; Sui, Chengjun ; Zhang, Xiaofeng

Macrophages play a multifaceted role in cancer biology, with both pro-tumorigenic and anti-tumorigenic functions. Understanding the mechanisms underlying macrophage involvement in cancer progression is essential for the development of therapeutic strategies. Our study analyzed single-cell RNA sequencing data from 12 patients with liver cancer and identified a subpopulation of macrophages characterized by elevated expression of SPP1, which correlates with poor prognosis in liver cancer patients. These SPP1⁺ macrophages induce upregulation of tumor stemness through a vitronectin (VTN)-dependent paracrine mechanism. Mechanistically, VTN derived from SPP1⁺ macrophages promote integrin αvβ5/adenosine 5'-monophosphate-activated protein kinase (AMPK)/Yes-associated protein 1 (YAP1)/SYR-box transcription factor 4 (SOX4) signaling, mediating liver tumor stemness and progression. Conversely, CCL15 produced by liver cancer cells drives polarization of M0 macrophages toward an SPP1⁺ macrophage phenotype, establishing a positive feedback loop of macrophage-tumor stemness. Furthermore, the presence of SPP1⁺ macrophages confers chemoresistance in liver cancer, and inhibition of the macrophage-tumor feedback loop through targeting integrin αvβ5/YAP1 signaling sensitizes liver cancer cells to chemotherapy. Our study highlights the crucial role of SPP1⁺ macrophages in liver cancer progression, providing novel insights for clinical liver cancer therapy.

17 Oct 2024·Advanced materials (Deerfield Beach, Fla.)

NIR-II Fluorescent Nanotheranostics with a Switchable Irradiation Mode for Immunogenic Sonodynamic Therapy.

Article

Author: Xiao, Haihua ; Liang, Ganghao ; Zhang, Hanchen ; Cui, Minhui ; Xu, Chun ; Tang, Dongsheng

Nanotheranostics, which integrate diagnostic and therapeutic functionalities, offer significant potential for tumor treatment. However, current nanotheranostic systems typically involve multiple molecules, each providing a singular diagnostic or therapeutic function, leading to challenges such as complex structural composition, poor targeting efficiency, lack of spatiotemporal control, and dependence on a single therapeutic modality. This study introduces NP^RBOXA, a nanoparticle functionalized with surface-bound cRGD for targeted delivery to α_vβ₃/α_vβ₅ receptors on tumor cells, achieving theranostic integration by sequentially switching its irradiation modes. Under 808 nm laser irradiation, NP^RBOXA emits NIR-II fluorescence, which aids in identifying the nanoparticle's location and fluorescence intensity, thereby determining the optimal treatment window. Following this, the irradiation mode switches to ultrasound irradiation at the optimal treatment window. Ultrasound irradiation induces NP^RBOXA to generate reactive oxygen species, promoting the reduction of OXA-IV to OXA-II, which in turn triggers immunogenic cell death. This mechanism enables a combination of sonodynamic therapy, chemotherapy, and immunotherapy for tumor treatment. The versatile design of NP^RBOXA holds promise for advancing precision oncology through enhanced therapeutic efficacy and real-time imaging guidance.

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