The goal of our study was to raise monoclonal antibodies (mAbs) against endothelial cell-surface proteins specific for tumor vasculature. Here, we describe the generation and intensive characterization of mAb AA98, including its functional properties and its antigen identification. In our study, an enhanced mAb AA98 immunoreactivity was observed on stimulated human umbilical vein endothelial cells (HUVECs). In addition, mAb AA98 showed remarkably restricted immunoreactivity against intratumoral neovasculature compared with blood vessels of normal tissues. We identified the AA98 antigen as human CD146, an adhesion molecule belonging to the immunoglobulin superfamily. Data from in vitro experiments imply structural and signaling functions for endothelial CD146; however, the role of CD146 in vivo is largely unknown. Here, we show that mAb AA98 displays antiangiogenic properties in vitro and in vivo. Proliferation and migration of HUVECs were inhibited by mAb AA98 as was angiogenesis in chicken chorioallantoic membrane (CAM) assays and tumor growth in 3 xenografted human tumor models in mice. Our data provide new insights into the function of CD146 on endothelial cells, validate CD146 as a novel target for antiangiogenic agents, and demonstrate that mAb AA98 has potential as a diagnostic and therapeutic agent in vascular and cancer biology. (Blood. 2003;102:184-191)

Current influenza vaccines only confer protection against homologous viruses. We synthesized pulmonary surfactant (PS)–biomimetic liposomes encapsulating 2′,3′-cyclic guanosine monophosphate–adenosine monophosphate (cGAMP), an agonist of the interferon gene inducer STING (stimulator of interferon genes). The adjuvant (PS-GAMP) vigorously augmented influenza vaccine–induced humoral and CD8+ T cell immune responses in mice by simulating the early phase of viral infection without concomitant excess inflammation. Two days after intranasal immunization with PS-GAMP–adjuvanted H1N1 vaccine, strong cross-protection was elicited against distant H1N1 and heterosubtypic H3N2, H5N1, and H7N9 viruses for at least 6 months while maintaining lung-resident memory CD8+ T cells. Adjuvanticity was then validated in ferrets. When alveolar epithelial cells (AECs) lacked Sting or gap junctions were blocked, PS-GAMP–mediated adjuvanticity was substantially abrogated in vivo. Thus, AECs play a pivotal role in configuring heterosubtypic immunity.

Constructing multicolor photoluminescence materials that allow for the integration of suitable external stimuli in order to control luminescence color conversions is a challenging objective. Multicolor luminescent output that is regulated in an in situ photo-controlled manner is not a common phenomenon. Herein, a photoluminescent supra­molecular assembly, prepared in two stages, is described that displays in situ photo-tuning broad-spectrum output. Benefiting from the reversible photo-switched constitutional interconversion of diaryl­ethenes, the fluorescence of a guest molecule, styryl­pyridinium-modified diaryl­ethene, can be switched on/off by alternating ultraviolet and visible light irradiation. Upon complexation of this guest with a host, cucurbit[8]­uril, the fluorescence intensity of the resulting binary supra­molecular nanofiber shows a drastic enhancement when compared with that of the free guest, which can also be quenched and recovered reversibly by light irradiation. Significantly, such cationic supra­molecular nanofibers also interact with anionic carbon dots to form broad-spectrum output ternary supra­molecular assemblies, the fluorescence of which can be changed efficiently from yellow to blue in an in situ photo-controlled manner. Pure white light emission can be realized expediently in the luminescence color-conversion process. The use of light as an external stimulus to regulate fluorescent color conversion provides us with an opportunity to design and construct more advanced anti-counterfeiting materials as well as visual display instruments.