This is a Platform Protocol to perform Phase II clinical trials in The Early Phase Pain Investigation Clinical Network (EPPIC-Net), under The Helping to End Addiction Long-termSM Initiative, or NIH HEAL InitiativeSM, related to the treatment of Painful Diabetic Peripheral Neuropathy (PDPN) in a platform setting to test multiple assets under a single protocol.

开始日期2022-09-21

申办/合作机构

National Institute of Neurological Disorders & Stroke

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100 项与吲哚醌相关的临床结果

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100 项与吲哚醌相关的转化医学

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100 项与吲哚醌相关的专利（医药）

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项与吲哚醌相关的文献（医药）

2025-03-01·Current Computer-Aided Drug Design

Computational Exploration of Isatin Derivatives for InhA Inhibition in Tuberculosis: Molecular Docking, MD Simulations and ADMET Insights

Article

作者: Dharamsi, Abhay ; Tripathi, Rati Kailash Prasad ; Patel, Vaishali Pavalbhai

Background::

Anti-tubercular drug discovery is a critical research area aimed at addressing the global health burden imposed by Mycobacterium tuberculosis. Nowadays, computational techniques have increased the likelihood of drug development compared to traditional, labor-intensive, and time-consuming drug design approaches. The pivotal goal of drug design is to identify compounds capable of selectively targeting protein, thereby disrupting its enzymatic activity. InhA, or NADH-dependent enoyl-acyl carrier protein reductase, stands at the forefront of targeted approaches in the battle against TB. Isatin derivatives have garnered interest for their diverse pharmacological activities.

Objective::

To identify novel isatin derivatives that could serve as potential chemical templates for anti-TB drug discovery by targeting InhA.

Methods::

The present work utilized various computational approaches, including molecular docking, binding free energy calculations, and conformational alignment studies to investigate the binding mode and interactions of carefully selected dataset of 88 isatin derivatives within InhA active site. Study also employed MD simulations of the most promising molecule to check the stability of the protein-ligand complex and in-silico ADMET profiling of the top compounds to predict their pharmacokinetic and toxicity properties.

Results::

Results provided insights into the structural features contributing to InhA inhibition, assessing overall drug-like characteristics of isatin derivatives and identified compound 48 (BA= -10.4 kcal mol-1) with potential for further optimization. MD simulation analysis revealed that compound 48 binds firmly within the InhA protein, exhibiting minimal conformational fluctuations and enhanced stability.

Conclusion::

Considering the aforementioned, isatin derivatives represents a novel framework for creating targeted InhA inhibitors during anti-TB therapy. However, experimental validations and in-depth analyses are crucial to confirm efficacy and safety of these derivatives as potential InhA inhibitors for TB treatment.

2025-01-01·PHYTOCHEMISTRY

Plant P450 forms indigo and indirubin when expressed in Escherichia coli

Article

作者: Anterola, Aldwin M ; Sagwan-Barkdoll, Laxmi ; Gang, David R. ; Kim, Min-Jeong ; Anterola, Aldwin M. ; Gang, David R ; Berim, Anna

Indigo and indirubin are derived from indoxyl molecules, which generally occur as indoxyl glycosides in woad (Isatis tinctoria L.) and other indigo-producing plants. Indoxyl glycosides are biosynthesized from indole via 3-hydroxylation to form indoxyl, followed by one or more glycosylations. Enzymes that attach and remove sugars to and from indoxyl have already been isolated and characterized, while enzymes that convert indole into indoxyl in plants have remained elusive, until the identification of P450s and flavin-containing monooxygenases that hydroxylate indole. A P450 gene from woad (named CYP71B102) was heterologously expressed in E. coli, resulting in the formation of indigo and indirubin, as well as isatin and 2-oxindole, which along with indoxyl are putative precursors of indirubin. The addition of either isatin or 2-oxindole to the recombinant E. coli reduced the levels of indigo and increased the amount of indirubin, whereas coexpression of CYP71B102 with isatin hydroxylase (which degrades isatin) increased the levels of indigo and decreased the amount of indirubin, albeit slightly. The results suggest that CYP71B102 hydroxylates indole at both the 2- and 3- positions to produce 2-oxindole and indoxyl, respectively, and that the coupling of indoxyl with either 2-oxindole or isatin forms indirubin, while dimerization of indoxyl forms indigo. This P450 gene is thus likely involved in the biosynthesis of indirubin in woad, as well as the formation of indigo and its glycosidic precursors, even if other types of enzymes, such as flavin-containing monooxygenases, may be involved in indole hydroxylation in other indigo-producing plants.

2025-01-01·CURRENT TOPICS IN MEDICINAL CHEMISTRY

Synthesis of Isatin-derived Heterocycles with Promising Anticancer Activities

Article

作者: Sharma, Aditi ; Banerjee, Bubun ; Singh, Arvind ; Kaur, Manmeet ; Priya, Anu

Isatin or 1H;-indole-2,3-dione skeleton has been playing a significant role in drug design and development. Isatin itself and many of its derivatives are widely distributed in naturally occurring bioactive compounds. Various synthetic isatin derivatives were found to possess a broad range of significant pharmacological efficacies especially anti-cancer activity against a wide variety of cancer cell lines. Interestingly, on a few occasions, some isatin-derived scaffolds were reported as more potent than the tested reputed drug molecules. As a result, isatin-derived compounds have been gaining significant attention in cancer-based drug developments. In this review, we have summarized literature reported during the last two decades related to the synthesis of structurally diverse isatin-derived scaffolds with promising anti-cancer activities.

项与吲哚醌相关的新闻（医药）

2024-11-16

·ioncology

血液国际谈丨Salomon Manier教授：医海泛舟，推陈出新，TIE-NDMM患者治疗方案持续优化升级

编者按近日，中国医师协会第十一届中法血液学学术会议在天津顺利召开，吸引到数百名国内外血液学领域的权威专家和学者齐聚一堂。会议期间，《肿瘤瞭望-血液时讯》特邀法国里尔大学医院血液学Salomon Manier教授就不适合移植的新诊断多发性骨髓瘤（TIE-NDMM）患者的当前治疗挑战、新兴治疗方案及老年虚弱患者群体中的管理进行了探讨。现将精粹整理成文，以飨读者。多发性骨髓瘤（MM）是一种常见的恶性血液肿瘤，尤其在老年人群中发病率较高。由于老年患者往往伴随着更多的并发症和较高的感染风险，其在治疗上的耐受性也相对较差。因此，针对这一特殊群体的治疗策略需要特别关注。在MM的治疗领域，我们正经历一个充满变革的时期，特别是在老年虚弱患者群体中。目前，对于TIE-NDMM患者，达雷妥尤单抗（Daratumumab）联合来那度胺（Lenalidomide）和地塞米松（Dexamethasone）的DRd方案已成为美国和欧洲的标准治疗方案。今年欧洲血液学会（EHA）大会上公布了一项多中心、随机、开放标签III期研究——MAIA的最终分析结果，探索了DRd三药联合方案治疗TIE-NDMM患者的疗效和安全性。研究数据显示，经过中位89.3个月的随访，DRd组患者的死亡风险降低了33%，中位生存期（mOS）超过7.5年，这是迄今为止TIE-NDMM临床研究报告中最长的OS数据，可谓是取得了里程碑式进展。尤为值得注意的是，该研究的虚弱亚组结果显示，与Rd（来那度胺联合地塞米松）两药方案相比，DRd三药方案可为老年虚弱NDMM患者带来显著的无进展生存期（PFS）获益（未达到 vs. 30.4个月，HR 0.62，P=0.003），且≥完全缓解率（43.6% vs. 30.8%）和微小残留病（MRD）阴性率（23.8% vs 10.1%）均进一步提高。MAIA研究结果证实了DRd方案在TIE-NDMM患者中疗效优越，为DRd方案成为TIE-NDMM的标准治疗方案之一提供了强有力的循证医学证据。基于MAIA研究结果，2024版NCCN指南、2024版Mayo指南、中国多发性骨髓瘤诊治指南（2022 修订版）等多项权威指南均推荐其作为TIE-NDMM患者的优选推荐方案。图1.MAIA研究最终OS结果随着对老年虚弱MM患者治疗研究的深入，我们正在从传统的统一治疗方案转向更加个性化的治疗策略。这种转变意味着我们需要根据患者的虚弱程度和年龄制定治疗方案。为了准确实施这种分层治疗模式，我们需要建立一个临床上可行的、标准统一的虚弱评估系统，这是目前亟待解决的问题。当前，多项临床试验正在探索去地塞米松方案在老年虚弱MM患者中的应用，以便降低毒性、控制感染风险，从而延长生存期并改善预后。如： 01 IFM 2017-03试验该试验探索了不含地塞米松的DR方案（达雷妥尤单抗联合来那度胺）治疗老年虚弱NDMM患者的疗效，中期分析结果显示，与Rd方案相比，DR方案可以带来更高的总缓解率（ORR）（96% vs 85%）、非常好的部分缓解率及以上（≥VGPR）（64% vs. 43%）以及MRD阴性率（10-5；10% vs. 3%），未观察到感染发生率（13% vs. 18%；P=0.29）的显著差异，两组间由于不良事件（AE）的治疗中断率也无显著差异（14% vs. 16%；P=0.65），证明了DR两药方案不仅保证了疗效，还降低了感染风险。目前，IFM 2017-03试验中期分析已经完成，期待即将公布的最终报告，以获得更多治疗方案的细节。同时，新一代免疫疗法在老年虚弱NDMM患者中的疗效的研究也正在陆续展开，如： 01 BENEFIT/IFM2020-05试验这是一项开放标签、多中心、平行对照的III期临床试验，旨在比较Isa-VRd（艾沙妥昔单抗+来那度胺+地塞米松+硼替佐米）四联疗法与IsaRd（艾沙妥昔单抗+来那度胺+地塞米松）三联疗法在TIE-NDMM患者中的疗效和安全性。初步分析结果显示，Isa-VRd方案在提高患者MRD阴性率方面表现出显著优势，这可能使以靶向CD38单克隆抗体艾沙妥昔单抗为基础的四联疗法成为未来不适合移植且年龄在65至79岁的NDMM患者的新标准治疗方案。 02 MajesTEC-7（NCT05552222）试验今年美国临床肿瘤学会（ASCO）年会上公布了这项III期试验的数据，旨在探索靶向CD3和B细胞成熟抗原（BCMA）的第一款双特异性抗体——特立妥单抗（Teclistamab）联合达雷妥尤单抗和来那度胺在26例不符合或不打算作为初始治疗进行自体干细胞移植的NDMM患者中的疗效。该试验的第一个安全性入组队列结果显示，这种三联疗法在NDMM患者中的ORR和PFS分别为92.3%和96.2%，显示出了早期的疗效结果和可控的安全性。尽管有30.8%的患者出现了3或4级的感染，但这些感染事件大多发生在前三个周期，强调了早期进行感染预防措施的必要性。 03 MagnetisMM-3（NCT04649359）试验这是一项开放标签、多中心、非随机、II期试验，评估了第二款CD3/BCMA双抗——埃纳妥单抗（Elranatamab）治疗复发/难治性MM（R/R MM）患者的疗效和安全性。试验结果显示：首次使用埃纳妥单抗作为BCMA靶向治疗的患者，其客观缓解率达58%，其中82%的患者能够维持至少9个月的缓解期；在中位随访时间为10.4个月时，这一患者亚群的客观缓解率为61%，证实了埃纳妥单抗对MM患者提供了更高的缓解率和更长的缓解持续时间。 04 CARTITUDE-4（NCT04181827）试验这项全球随机开放标签的III期研究评估了靶向BCMA的嵌合抗原受体T细胞（CAR-T）疗法——西达基奥仑赛与泊马度胺、硼替佐米和地塞米松（PVd）或达雷妥尤单抗、泊马度胺和地塞米松（DPd）在复发且来那度胺耐药的MM患者中的疗效和安全性。该研究取得了具有统计学意义和临床意义的总生存期（OS）改善。值得注意的是，在试验组中，西达基奥仑赛的治疗时长是预先设定的，这与以往对老年患者通常采用的持续治疗模式不同。这种固定时长的治疗策略为老年患者提供了一种新的治疗选择，有可能实现治疗的停止，从而改善他们的生活质量。总之，多发性骨髓瘤的治疗正朝着更加个性化和精准的方向发展。随着新治疗方案的不断涌现和临床试验的深入，我们有望为老年虚弱患者提供更多、更有效的治疗选择，同时提高他们的生活质量并改善预后。未来的研究将继续探索如何更好地为老年虚弱患者提供个性化的治疗，以实现最佳的治疗效果和生活质量。（上下滑动查看英文原文） Multiple myeloma (MM) is a common malignant hematological tumor, particularly prevalent among the elderly population. Due to the presence of more comorbidities and a higher risk of infection in elderly patients, their tolerance to treatment is relatively poor. Therefore, treatment strategies for this special group require special attention. In the field of MM treatment, we are experiencing a transformative period, especially in the elderly and frail patient population. Currently, for transplant-ineligible newly diagnosed multiple myeloma (TIE-NDMM) patients, the DRd regimen combining daratumumab, lenalidomide, and dexamethasone has become the standard treatment in the United States and Europe. This year at the European Hematology Association (EHA) Congress, the final analysis results of the multicenter, randomized, open-label phase III MAIA study[1] were announced, exploring the efficacy and safety of the DRd triplet regimen in TIE-NDMM patients. The study data showed that after a median follow-up of 89.3 months, the death risk of patients in the DRd group was reduced by 33%, and the median overall survival (mOS) exceeded 7.5 years. This is the longest OS data reported in TIE-NDMM clinical studies to date, marking a milestone achievement. Notably, the frail subgroup results of the study indicated that compared to the Rd two-drug regimen, the DRd triplet regimen brought significant progression-free survival (PFS) benefits to elderly frail NDMM patients (not reached vs. 30.4 months, HR 0.62, P=0.003), and both the ≥ complete response rate (43.6% vs. 30.8%) and minimal residual disease (MRD) negativity rate (23.8% vs. 10.1%) were further improved. The MAIA study results confirmed the superior efficacy of the DRd regimen in TIE-NDMM patients, providing strong evidence-based medical evidence for the DRd regimen to become one of the standard treatment options for TIE-NDMM. Based on the MAIA study results, the 2024 NCCN guidelines, the 2024 Mayo Clinic guidelines, the Chinese Guidelines for the Diagnosis and Treatment of Multiple Myeloma (2022 revised edition), and other authoritative guidelines all recommend it as the preferred option for TIE-NDMM patients. As research on the treatment of elderly frail MM patients deepens, we are transitioning from traditional uniform treatment plans to more personalized treatment strategies. This shift means that we need to develop treatment plans based on the degree of frailty and age of the patients. To accurately implement this stratified treatment model, we need to establish a clinically feasible and standardized frailty assessment system, which is an issue that needs to be addressed urgently. Currently, several clinical trials are exploring the application of dexamethasone-free regimens in elderly frail MM patients to reduce toxicity, control the risk of infection, thereby extending survival and improving prognosis. For example: IFM 2017-03 trial: This trial explored the efficacy of the dexamethasone-free DR regimen (daratumumab combined with lenalidomide) in treating elderly frail NDMM patients. The interim analysis results showed that compared with the Rd regimen (lenalidomide combined with dexamethasone), the DR regimen brought a higher overall response rate (ORR) (96% vs. 85%), very good partial response rate and above (≥VGPR) (64% vs. 43%), and MRD negativity rate (10-5; 10% vs. 3%). No significant difference in infection incidence (13% vs. 18%; P=0.29) was observed, and there was no significant difference in treatment discontinuation rates due to adverse events (AE) between the two groups (14% vs. 16%; P=0.65), proving that the DR two-drug regimen not only ensures efficacy but also reduces the risk of infection. The interim analysis of the IFM 2017-03 trial has been completed, and we look forward to the upcoming final report for more treatment details. At the same time, studies on the efficacy of the new generation of immunotherapies in elderly frail NDMM patients are also being carried out, such as: BENEFIT/IFM2020-05 trial: This is an open-label, multicenter, parallel-controlled phase III clinical trial aimed at comparing the efficacy and safety of the Isa-VRd (isatuximab + lenalidomide + dexamethasone + bortezomib) quadruplet regimen with the IsaRd (isatuximab + lenalidomide + dexamethasone) triplet regimen in TIE-NDMM patients. Preliminary analysis results showed that the Isa-VRd regimen showed a significant advantage in improving the MRD negativity rate of patients, which may make the isatuximab-based quadruplet regimen a new standard treatment option for NDMM patients aged 65 to 79 who are not suitable for transplantation. MajesTEC-7 (NCT05552222) trial: At this year's American Society of Clinical Oncology (ASCO) annual meeting, data from this phase III trial were announced, exploring the efficacy of the first bispecific antibody targeting CD3 and B-cell maturation antigen (BCMA) - teclistamab, combined with daratumumab and lenalidomide in 26 NDMM patients who are not eligible or do not intend to undergo autologous stem cell transplantation as initial treatment. The first safety cohort results of this trial showed that the overall response rate and progression-free survival rate of this triplet regimen in NDMM patients were 92.3% and 96.2%, respectively, showing early efficacy results and controllable safety. Although 30.8% of patients had grade 3 or 4 infections, most of these infection events occurred in the first three cycles, emphasizing the need for early infection prevention measures. MagnetisMM-3 (NCT04649359) trial: This is an open-label, multicenter, non-randomized, phase II trial evaluating the efficacy and safety of the second CD3/BCMA bispecific antibody - elranatamab, in treating relapsed/refractory multiple myeloma (R/R MM) patients. The trial results showed that for patients who used elranatamab as BCMA-targeted therapy for the first time, the objective response rate was 58%, with 82% of patients maintaining a response for at least 9 months; at a median follow-up time of 10.4 months, the objective response rate for this patient subgroup was 61%, confirming that elranatamab provided a higher response rate and longer duration of response for MM patients. CARTITUDE-4 (NCT04181827) trial: This global randomized open-label phase III study evaluated the efficacy and safety of the BCMA-targeted chimeric antigen receptor T-cell (CAR-T) therapy - ciltacabtagene autoleucel (cilta-cel) compared with pomalidomide, bortezomib, and dexamethasone (PVd) or daratumumab, pomalidomide, and dexamethasone (DPd) in relapsed and lenalidomide-resistant MM patients. The study achieved a statistically and clinically significant improvement in overall survival (OS). It is worth noting that in the experimental group, the treatment duration of cilta-cel was preset, which is different from the continuous treatment mode usually adopted for elderly patients. This fixed-duration treatment strategy provides a new treatment option for elderly patients, potentially allowing for the cessation of treatment and thus improving their quality of life. In summary, the treatment of multiple myeloma is moving towards a more personalized and precise direction. With the continuous emergence of new treatment regimens and in-depth clinical trials, we hope to provide more and more effective treatment options for elderly frail patients, while improving their quality of life and prognosis. Future research will continue to explore how to better provide personalized treatment for elderly frail patients to achieve the best treatment effects and quality of life. 专家简介 Salomon Manier教授法国里尔大学医院血液学副教授美国血液学会 (ASH)、欧洲血液学会 (EHA)、国际骨髓瘤学会 (IMS)、法国血液学会 (SFH) 成员、法语国家骨髓瘤学会 (IFM) 董事会成员 ASH 浆细胞肿瘤科学委员会和美国癌症研究协会 (AACR) 骨髓瘤科学委员会成员（来源：《肿瘤瞭望–血液时讯》编辑部）声明凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

临床结果临床3期

2023-03-01

·BioSpace

Peer-Reviewed Publication Shows Superiority of Moximed’s MISHA™ Knee System

Implantable Shock Absorber (ISA) relieves pain and improves function in patients not ready for joint replacement FREMONT, Calif.--(BUSINESS WIRE)-- Moximed, a medical device company on a mission to improve the standard of care for people with knee osteoarthritis (OA), today announced the publication of a peer-reviewed article of the MISHA™ Knee System, an implantable shock absorber (ISA) for the knee. The two-year pivotal IDE study results and superiority of the primary endpoint of the Calypso Study of the MISHA Knee System were published in Cartilage.1 In the study, the MISHA Knee System was superior to high tibial osteotomy (HTO) when evaluated against a two-year composite endpoint, demonstrating pain relief, functional improvement, and a positive safety pro patients with medial knee OA. Major findings from the study include: Outpatient Surgery and Early Recovery: 90.5% of U.S. patients were discharged in under 24 hours, and the overall study population returned to full weight-bearing without assist devices by an average 13 days. High Responder Rates: 95.8% of patients treated with an ISA reported clinically meaningful pain relief at two years. Substantial Improvement: At 24 months, patients reported an average of 76% reduction in pain and 74% improvement in function compared to baseline levels. Favorable Safety: 95% of ISA patients were free from an endpoint safety event, and 100% of ISA devices were free from mechanical failure. “The MISHA Knee System achieved its IDE study primary endpoint with superiority. The investigators and I are pleased to report complete details of the clinical study, which was designed specifically to meet a rigorous FDA hurdle,” stated David R. Diduch, MD, the A.F. Voshell Professor of Sports Medicine, Department of Sports Medicine, University of Virginia. “The results demonstrated that nearly all the patients who received the MISHA Knee System experienced clinically meaningful pain relief at two years, and the safety pro the device and procedure were comparable to a well-established surgical control. I anticipate many surgeons and patients will be excited to learn about this technology.” About Osteoarthritis Osteoarthritis (OA) is a common, debilitating condition, affecting the lives of over 32 million adults in the U.S, and projected to impact 70 million Americans by 2040. Knee OA develops when the joint’s natural shock absorbers, cartilage and meniscus, no longer cushion the joint from daily activities, leading to chronic pain and activity limitation. Many people with mild to moderate OA are otherwise healthy, in their prime working years, and have busy lives to live. For these patients, total knee replacement is a reluctant option, as it is an end-stage treatment for end-stage disease. OA patients without end-stage disease seek options that preserve their knee, activity level, and quality of life. About Moximed Moximed was founded in 2008 and is dedicated to helping people with mild to moderate osteoarthritis preserve their knee joints while living healthy, active lives. The company’s technology, the MISHA™ Knee System, is the result of over a decade of clinical research and development and is the first implantable shock absorber being developed for the treatment of medial compartment knee osteoarthritis (OA). With experienced medtech leadership and strong investor support, Moximed is poised to elevate the standard of care and quality of life for millions of pre-arthroplasty knee OA sufferers hindered by arthritic knee pain and function loss. Moximed is based in Fremont, California. About The MISHA™ Knee System Reducing weight on painful osteoarthritic joints is known to reduce pain and improve function. The MISHA™ Knee System being developed is the first implantable shock absorber that reduces weight on the knee joint with every walking step, easing pain, preserving function, and possibly delaying joint replacement surgery. The implant is placed on the medial knee and moves with the natural joint, reducing about 30% of the peak force on the knee with every walking step.2 1 Diduch DR, Crawford DC, Ranawat AS, Victor J, Flanigan DC. Implantable Shock Absorber Provides Superior Pain Relief and Functional Improvement Compared with High Tibial Osteotomy in Patients with Mild-to-Moderate Medial Knee Osteoarthritis: A 2-Year Report. CARTILAGE. 2023;0(0). doi:10.1177/19476035231157335. 2 Morgan OJ, Hillstrom HJ, Ranawat A, Fragomen AT, Rozbruch SR, Hillstrom R. Effects of a Medial Knee Unloading Implant on Tibiofemoral Joint Mechanics During Walking. J Orthop Res. 2019;37(10):2149-2156. doi:10.1002/jor.24379.

临床结果

2022-11-08

·PRNewswire

First-in-Human Study: Amplivant® Adjuvant Boosts Immune Response of Synthetic Long Peptide Immunotherapy

First-in-human study investigating the safety and immunogenicity of ISA's proprietary Amplivant adjuvant conjugated to human papillomavirus type 16 (HPV16) Synthetic Long Peptides (SLPs). SLPs conjugated to Amplivant elicit a significant, strong immune response and dose related systemic T cell immunity when injected intradermally. Study demonstrates that SLPs conjugated to Amplivant have highly favourable tolerability and safety when used as an intradermal therapeutic vaccine. OEGSTGEEST, The Netherlands, Nov. 8, 2022 /PRNewswire/ -- ISA Pharmaceuticals B.V., a clinical stage biotech company developing immunotherapies to treat cancers and infectious diseases, is delighted to announce publication by Leiden University Medical Center (LUMC) of a phase 1 clinical study using ISA's proprietary Amplivant® adjuvant and Synthetic Long Peptide (SLP®) therapeutic vaccine technology. The study was recently published in the Journal for ImmunoTherapy of Cancer. This open access paper is entitled 'Intradermal vaccination of HPV-16 E6 synthetic peptides conjugated to an optimized Toll-like receptor 2 ligand shows safety and potent T cell immunogenicity in patients with HPV16 positive (pre-)malignant lesions' and can be found at: . Amplivant is a molecularly optimized Toll-like receptor 1/2 ligand that can be covalently conjugated to tumour peptide antigens. In preclinical models Amplivant-adjuvanted SLPs strongly enhance antigen presentation by dendritic cells, T cell priming, and induce effective antitumor responses. This first-in-human clinical study demonstrated a favourable safety profile without serious adverse events and a strong immune response generated with only two Amplivant-conjugated HPV16 SLPs. The study concludes that Amplivant-conjugated SLPs can be safely used as an intradermal therapeutic vaccine to induce HPV16-specific T cell immunity in previously treated patients with HPV16-positive (pre-)malignancies. Vaccine dose escalation in 25 patients caused a corresponding increase in systemic T cell immunity. Amplivant was conjugated to two SLPs derived from the two most immunodominant regions of the HPV16 E6 oncoprotein. Patients received 3 doses intradermally, three times a week, and with a 3-week interval in four dose groups (1, 5, 20 or 50 µg per conjugated peptide). Peptide-specific T cell immune responses were determined in PBMC's from blood samples taken before, during and after vaccination. Details of the study can be found on clinicaltrials.gov under the identifier NCT02821494. About ISA Pharmaceuticals ISA Pharmaceuticals is an immunotherapy company developing treatments for various cancers and infectious diseases. ISA has best-in-class technology to stimulate and activate the human immune system, specifically T cells, to fight diseased or infected cells. Its lead asset ISA101b is in late-stage clinical trials for human papillomavirus type 16 (HPV16)-induced cancers in a collaboration with biotechnology company Regeneron. Other assets are in preclinical stage development and include immunotherapies to treat patients that suffer from cancers that over-express PRAME, chronic hepatitis B or SARS-CoV2 infections. For more information, please visit . About AMPLIVANT® ISA's AMPLIVANT® technology comprises a proprietary and synthetic Toll-Like Receptor (TLR) 1/2 ligand with enhanced immunostimulatory activity that can be coupled to the peptide in the standard SLP® manufacturing process. AMPLIVANT®-conjugated immunotherapeutics allow lower dosing at higher efficacy through better dendritic cell antigen processing and presentation as well as enhanced T cell priming. This technology is not only applicable to all SLP® immunotherapeutics, but also to any other type of targeted immunotherapy to potentially enhance treatment efficacy. AMPLIVANT® is registered as a trademark in Europe. SOURCE ISA Pharmaceuticals

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适应症	最高研发状态	国家/地区	公司	日期
帕金森病	临床申请	中国	武汉康丽源医药科技有限公司	2013-01-09
帕金森病	临床申请	中国	武汉光谷新药孵化公共服务平台有限公司	2013-01-09
帕金森病	临床申请	中国	青岛大学	2013-01-09