Introduction: The use of monoclonal antibodies is one of the strategies for targeting the specific key points of the main pathways of cancer growth and survival, but only a few antibodies have offered a clear clinical benefit in the treatment of non-haematological malignancies. Areas covered: This review summarizes the general properties of monoclonal antibodies, including structure, nomenclature and production techniques. The antibodies approved for use in clinical practice for the treatment of non-haematological tumors and those antibodies still being developed in this setting are briefly described. The types of antibody fragments are also reported. Expert opinion: Monoclonal antibodies were initially developed in order to avoid the cytotoxic effects of chemotherapy on healthy tissues. However antibodies have not yet replaced chemotherapy agents, since the combination of both kinds of drugs have usually appeared to achieve higher benefit compared with chemotherapy alone. The research for the development of new monoclonal antibodies aims to identify further targets and to provide innovative antibody constructs. 相似文献
AIM: To investigate the anti-inflammatory effect of intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) in patients with macular edema secondary to retinal vein occlusion (RVO-ME).
METHODS: Twenty-eight eyes from twenty-eight treatment-naïve patients (14 males and 14 females) with RVO-ME were included in this retrospective study. The retinal vein occlusion (RVO) was comprised of both central retinal vein occlusion (CRVO, n=14) and branch retinal vein occlusion (BRVO, n=14). Intravitreal injection of anti-VEGF reagents were administered monthly for three consecutive months, in which 18 patients were injected with ranibizumab and 10 patients were injected with conbercept. All eyes were imaged with optical coherence tomography angiography (OCTA) at baseline and 1wk after monthly intravitreal anti-VEGF injection. The visual acuity (VA), central macular thickness (CMT), the number of hyperreflective foci (HRF) recognized as an inflammatory sign in OCT images, and non-perfusion area (NPA), were compared before and after anti-VEGF treatments.
RESULTS: The mean interval between baseline and follow-up was 29.4±0.79 (range, 27-48)d. Compared with the baseline, the VA improved (logMAR 1.5±0.1 vs 0.8±0.1, P<0.05) and CMT decreased (460±34.0 μm vs 268.8±12.0 μm, P<0.05), significantly, after anti-VEGF treatment. The number of HRF was decreased significantly (76.5±4.8 vs 47.8±4.3, P<0.05) after anti-VEGF treatment.
CONCLUSION: Anti-VEGF therapy is effective in treating RVO-ME. The mechanisms for the decreased HRF and the reduction of NPA by anti-VEGF therapy merits further exploration. 相似文献
AIM: To analyze concentrations of vascular endothelial growth factor (VEGF) and fibrosis-related factors in vitreous fluid of proliferative diabetic retinopathy (PDR) patients pre-treated with intravitreal anti-VEGF injections (IVI) at different time periods prior to pars plana vitrectomy (PPV), and their correlation with the degree of vitreoretinal fibrosis and explore the optimal timing of preoperative IVI.
METHODS: The prospective case-control study from January 2019 to July 2020 included 31 eyes with PDR-related complications (PDR group) and 21 eyes with non-diabetic ocular disease (control group) requiring PPV. PDR eyes were divided into four groups based on timing of PPV: 3d after IVI (3-day group); 5d after IVI (5-day group); 7 or more days after IVI (≥7-day group); and no IVI. Vitreous fluid samples (0.5-1.0 mL) were collected prior to switching on the infusion before routine 23-G PPV. Concentrations of VEGF, basic fibroblast growth factor (bFGF), periostin (PN), interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α were measured by immunoassay, and concentration differences for each cytokine were compared among the groups. The degree of vitreoretinal fibrosis was graded intraoperatively, and the correlation between the changes in cytokine levels and the severity of vitreoretinal fibrosis was analyzed by univariate ordinal logistic regression analysis.
RESULTS: PDR eyes without IVI had significantly higher VEGF, bFGF, PN, and IL-6 concentrations than non-diabetic eyes (all P<0.05), and had a significantly higher concentration of VEGF (P<0.05) and a significantly lower concentration of IL-8 (P<0.05) than PDR eyes with IVI. Statistically significant differences were also observed for concentrations of VEGF, bFGF, PN, IL-6, and IL-8 among 3-day, 5-day, and ≥7-day groups (all P<0.05); meanwhile there was no significant difference in TNF-α among groups (P=0.226). The 5-day group had the lowest concentration of VEGF and the ≥7-day group had the highest concentration of bFGF and PN. The degree of vitreoretinal fibrosis was significantly higher in the ≥7-day group compared to the 3-day (P=0.015) and 5-day group (P=0.039), and vitreoretinal fibrosis correlated significantly with concentrations of bFGF, PN, IL-6, and IL-8 (all P<0.05). Univariate ordinal logistic regression analysis showed that bFGF was an independent risk factor for the severity of vitreoretinal fibrosis in PDR patients pre-treated with IVI.
CONCLUSION: The vitreous concentrations of VEGF, bFGF, PN, IL-6, and IL-8 change after pretreatment with IVI before PPV in PDR patients. The degree of vitreoretinal fibrosis is higher in patients with a longer time between IVI treatment and PPV, which may be related to the angio-fibrosis switch. The results suggest that PPV should be performed 5d after IVI administration in PDR patients. 相似文献
Purpose: Intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents including ranibizumab and aflibercept are used to treat patients with ocular disorders such as neovascular age-related macular degeneration (nAMD); however, the injections are associated with rare instances of severe ocular inflammation. This study compared severe ocular inflammation rates in patients treated with ranibizumab versus aflibercept.
Methods: United States physician-level claims data covering an 18-month period for each therapy were analyzed. The primary analysis compared severe ocular inflammation event rates per 1000 injections. Sensitivity and subgroup analyses evaluated the impact of factors including intraocular surgery, intravitreal antibiotic administration, and previous intravitreal injections.
Results: The analysis included 432,794 injection claims (ranibizumab n = 253,647, aflibercept n = 179,147); significantly, more unique severe ocular inflammation events occurred in patients receiving aflibercept than ranibizumab (1.06/1000 injections, 95% confidence interval [CI], 0.91–1.21, vs. 0.64/1000 injections, 95% CI 0.54–0.74; p < 0.0001). Comparable results were observed for analyses of patients who had undergone glaucoma or cataract surgeries, had antibiotic-associated endophthalmitis, had non-antibiotic-associated endophthalmitis, and were non-treatment-naive. In contrast, no significant differences in severe ocular inflammation claims were recorded in treatment-naive patients who had no record of anti-VEGF treatment in the 6 months preceding the index claim. No significant change occurred in the rate of severe ocular inflammation claims over time following ranibizumab treatment.
Conclusions: Severe ocular inflammation was more frequent following intravitreal injection with aflibercept than with ranibizumab during routine clinical use in patients with nAMD. This highlights the importance of real-world, post-approval, observational monitoring of novel medicines, and may aid clinical decision-making, including choice of anti-VEGF agent. 相似文献
A pterygium is a very common conjunctival degenerative condition. It has been well established that there are different factors that are interrelated and involved in the growth of pterygia. Historically described more as a degenerative process, inflammation and fibrovascular proliferation have proven to be very important factors. Many studies have shown VEGF to be increased in the pathogenesis of pterygia. There are a variety of options for the management of pterygium. The over expression of VEGF in pterygium tissue led us to develop anti-angiogenic/anti-VEGF therapy which could induce regression of blood vessels and hence retard progression of pterygium. The role of angiogenesis and of VEGF in ocular pathology is established including in corneal neovascularization, specifically in pterygial tissue. Evidence suggests that local bevacizumab may be effective in treatment of ocular surface neovascularization. Currently, data in the use of subconjunctival bevacizumab in the treatment of pterygia are not conclusive. New anti-angiogenic therapies will hopefully focus more on facilitating delivery into tissue, increasing the duration of effect while continuing to minimize adverse side effects. 相似文献
AIM: To determine the effect of multiple injections of ranibizumab or bevacizumab on retinal nerve fiber layer (RNFL) and intraocular pressure (IOP) in patients with age-related macular degeneration (AMD).METHODS:This retrospective study includes 35 eyes of 35 patients treated with intravitreal bevacizumab (IVB, 1.25mg/0.05mL) and 30 eyes of 30 patients with intravitreal ranibizumab (IVR, 0.5mg/0.05mL) who had Fast RNFL analysis (Stratus?); IOP measurements were taken 30 minutes and 24 hours after each injection.RESULTS:The mean ages were 68.0±7.5 and 69.1±7.7 years in the IVR and IVB groups, respectively (P=0.55). They underwent (6.3±1.9) and (5.1±1.3) injections (P=0.07) over (13.6±2.1) and (14.05±2.6) months (P=0.45) in the IVR and IVB groups, respectively. Changes in overall and temporal RNFL thickness in IVR-treated eyes (105.3±6.9µm and 74.4±11.2µm) were not different from those in untreated eyes in the IVR group (104.6± 8.4µm and 75.1±12.6µm) (P=0.57 and P=0.41, respectively). Similarly, overall and temporal RNFL thickness in IVB-treated eyes (105.8±8.1µm and 74.5±11.8µm) were not different from those in untreated eyes in the IVB group (104.6±8µm and 74.8±12.9µm) (P=0.42 and P=0.80, respectively). The frequencies of IOP rise (P=0.60) and changes in RNFL thickness from baseline (P=0.16) were comparable between groups.CONCLUSION:Repeated intravitreal injection of ranibizumab or bevacizumab does not seem have adverse effects on RNFL thickness or IOP in wet AMD patients. 相似文献
Introduction: Targeted agents have dramatically improved and enriched the therapeutical choices for patients with metastatic colorectal cancer (mCRC). By better understanding the role of the angiogenic pathway in colorectal cancer (CRC), new therapies have been developed. Bevacizumab, the first anti-angiogenetic agent approved for the treatment of mCRC provide a proof of concept since it has improved the progression-free survival and overall survival when combined with cytotoxic chemotherapy. Areas covered: This review is focused on the most recent findings on the VEGF signaling pathway and new therapeutic drugs explored in clinical trials. Expert opinion: Despite the advantage offered by bevacizumab, the median overall survival of mCRC patient exceeds 21 months; thus, investigational efforts are needed. Several antiangiogenic agents for the treatment of mCRC are being tested in preclinical and clinical Phase I/II trials. Unfortunately a discrete number of Phase III trials produced negative results. Recently aflibercept and regorafenib, two new antiangiogenic drugs, have been approved as the new-targeted agents for the treatment of mCRC, according to the positive findings from the VELOUR and the CORRECT studies. In order to maximize clinical impact it will be important to validate predictive biomarkers and best combination treatments to offer for mCRC patients; further research and intense investigation is still required. 相似文献
Introduction:Treatment of colorectal cancer (CRC) has changed dramatically over the past decade, mainly due to the advent of molecularly targeted agents. In particular, an improved understanding of the role of the angiogenesis pathway in CRC has led to advancements in treatment. Bevacizumab has been shown to improve the progression-free survival and overall survival when combined with cytotoxic chemotherapy in patients with metastatic CRC (mCRC) and at present is the only antiangiogenesis agent approved for the treatment of this cancer. Areas covered: In this review, the authors outline the most recent data on the VEGF signaling pathway and on new therapeutic reagents that target it, provide insight into their mechanisms, and describe results from recent clinical trials. Expert opinion: In the new decade of ‘modern therapy', an increasing number of antiangiogenic agents for the treatment of mCRC are being tested in preclinical models, and dozens of studies on these drugs are ongoing. Presently, eight novel antiangiogenic agents are in Phase III trials and a wide range of other candidates are being tested in Phase I/II trials. Given the preliminary positive results of two recent Phase III trials, aflibercept and regorafenib, probably, will be new-targeted agents approved for the treatment of mCRC. Furthermore, the list of potentially approved agents seems to increase in the next years and to maximize their potential clinical impact, is critically important to introduce efficient molecular diagnostic methodologies into the drug development process to indentify the subset of patients who would benefit most from their use. 相似文献