To date, more than 30 antibodies have been approved worldwide for therapeutic use. While the monoclonal antibody market is rapidly growing, the clinical use of therapeutic antibodies is mostly limited to treatment of cancers and immunological disorders. Moreover, antibodies against only five targets (TNF-α, HER2, CD20, EGFR, and VEGF) account for more than 80 percent of the worldwide market of therapeutic antibodies. The shortage of novel, clinically proven targets has resulted in the development of many distinct therapeutic antibodies against a small number of proven targets, based on the premise that different antibody molecules against the same target antigen have distinct biological and clinical effects from one another. For example, four antibodies against TNF-α have been approved by the FDA -- infliximab, adalimumab, golimumab, and certolizumab pegol -- with many more in clinical and preclinical development. The situation is similar for HER2, CD20, EGFR, and VEGF, each having one or more approved antibodies and many more under development. This review discusses the different binding characteristics, mechanisms of action, and biological and clinical activities of multiple monoclonal antibodies against TNF-α, HER-2, CD20, and EGFR and provides insights into the development of therapeutic antibodies. 相似文献
A tumor‐selective drug delivery nanogel with redox‐responsive size swelling and co‐instantaneous drug release is developed. The nanogel is formed by poly(ethylene glycol) diglycidyl ether and cystamine double crosslinked hyaluronic acid (HA). The disulfide bond in cystamine (Cys) is in charge of the responsiveness, while the compact polymer network turns the nanogel a capsule for effective drug loading. The tumor targeting is achieved by the known HA‐receptor mediated endocytosis. The responsive swelling of this nanogel and co‐instantaneous drug releases happen with the cleavage of the disulfide bond following tumor targeting and cell endocytosis, which is triggered by massive glutathione (GSH) in the cytoplasm of tumor cells. The highly selective nanogel uptake by tumor cells is directly demonstrated by fluorescence microscopy and flow cytometry. The dynamic light scattering and fluorescent spectrum reveal the GSH‐triggered size change and simultaneous drug release, which results in higher tumor cytotoxicity and over fourfold efficacy against tumor cells compared with normal cells. These results indicate that these HA‐PEG‐Cys‐DOX nanogels, with performance of selective drug delivery, intracellular reconstruction, and responsive drug release, are promising platforms for better therapeutic effects in cancer treatment. 相似文献
Photothermal therapy (PTT) is an emerging noninvasive and precise localized therapeutic modality; however, it is deeply limited by its poor tumor accumulation, inadequate photothermal conversion efficiency, and the thermoresistance of cancer cells. Aimed at these shortcomings, tumor‐targeting nanoparticles (iRGD‐W18O49‐17AAG) comprising carboxyl‐group‐functionalized W18O49 nanoparticles, integrin‐targeting peptide iRGD, and HSP90‐inhibitor 17AAG are developed. The W18O49 nanoparticles act as excellent PTT carriers and computed tomography (CT) imaging contrast agents. The ring type polypeptide iRGD promotes the accumulation of nanoparticles in the tumour and further penetration into cancer cells. The introduction of 17AAG can inhibit the heat‐shock response and overcome the thermoresistance, thus increasing the curative effect of PTT and reducing the chance of tumor recurrence. The W18O49 nanoparticles can also be used to monitor and guide the phototherapeutic through CT and near‐infrared fluorescence imaging after modification with Cy5.5. In addition, superior biosafety is also indicated in both preliminary in vitro and in vivo assessments. The potential of iRGD‐W18O49‐17AAG in tumor targeting, dual modality imaging‐guided and remarkable enhanced PTT of gastric cancer with ignorable side effect both in vitro and in vivo, which may be further applied in clinic, is highlighted. 相似文献
The development of early and personalized diagnostic protocol with rapid response and high accuracy is considered the most promising avenue to advance point-of-care testing for tumor diagnosis and therapy. Given the growing awareness of the limitations of conventional tissue biopsy for gathering tumor information, considerable interest has recently been aroused in liquid biopsy. Among a myriad of analytical approaches proposed for liquid biopsy, microfluidics-based separation and purification techniques possess merits of high throughput, low samples consumption, high flexibility, low cost, high sensitivity, automation capability and enhanced spatio-temporal control. These characteristics endow microfluidics to serve as an emerging and promising tool in tumor diagnosis and prognosis by identifying specific circulating tumor biomarkers. In this review, we will put our focus on three key categories of circulating tumor biomarkers, namely, circulating tumor cells (CTCs), circulating exosomes, and circulating nucleic acids (cNAs), and discuss the significant roles of microfluidics in the separation and analysis of circulating tumor biomarkers. Recent advances in microfluidic separation and analysis of CTCs, exosomes, and cNAs will be highlighted and tabulated. Finally, the current challenges and future niches of using microfluidic techniques in the separation and analysis of circulating tumor biomarkers will be discussed. 相似文献
Even though the diagnostic and prognostic value of circulating tumor cells (CTCs) has been demonstrated, their clinical utility and widespread adoption have been limited. Herein, we describe a new device, size‐dictated immunocapture chip (SDI‐Chip), for efficient, sensitive, and spatially resolved capture and detection of CTCs. SDI‐Chip enables selective, frequent, and extended interaction of CTCs with hydrodynamically optimized immunocoated micropillar surfaces. CTCs with different antigen expression levels can be efficiently captured and spatially resolved around the micropillars. Capture efficiency greater than 92 % with a purity of 82 % was achieved with blood samples. CTCs were detected in non‐metastasis colorectal (CRC) patients, while none was detected from healthy volunteers. We believe that SDI‐Chip will facilitate the transition of tumor diagnosis from anatomical pathology to molecular pathology in localized CRC patients. 相似文献
The fabrication of nanodiamond (ND)‐based drug carriers for tumor‐targeted drug delivery is described. The ND clusters with an average size of 52.84 nm are fabricated using a simple fluidic device combined with a precipitation method and then conjugated with folic acid (FA) and doxorubicin (Dox) via carbodiimide chemistry to obtain FA/Dox‐modified ND (FA/Dox‐ND) clusters. Cell culture experiments revealed that KB (folate receptor‐positive) cells are preferentially ablated by FA/Dox‐ND clusters compared to A549 (folate receptor‐negative) cells. In vivo results revealed that FA/Dox‐ND clusters are specifically accumulated in tumor tissues after intravenous injection into tumor‐bearing mice, effectively reducing the volume of tumor. Based on these results, this study suggests that FA/Dox‐ND clusters can be a good candidate as tumor‐targeted nanovehicles for delivery of antitumor drug.
