A Multi-Center Randomised Open-Label Phase 2 Study to Assess the Safety, Tolerability and Efficacy of Fimaporfin-Induced Photochemical Internalisation of Gemcitabine Complemented by Gemcitabine/Cisplatin Chemotherapy Versus Gemcitabine/Cisplatin Alone in Patients With Inoperable Cholangiocarcinoma

This study will assess the safety and effectiveness of fimaporfin-induced photochemical internalisation (PCI) of gemcitabine complemented by systemic gemcitabine/cisplatin chemotherapy compared to gemcitabine/cisplatin alone, in patients with inoperable cholangiocarcinoma (CCA). Participants will be randomly assigned to one of the treatment groups and will receive study treatment for 6 months, followed by assessments every 3 months, as applicable.

开始日期2019-05-23

申办/合作机构

PCI Biotech AS

NCT02947854

/ Completed临床1期

An Open-label, Phase I/Proof of Principle, Dose Escalation Study to Assess Safety, Tolerability and Immune Response of Fimaporfin-induced Photochemical Internalisation (PCI) of Antigen/Adjuvant in Healthy Male/Female Subjects

Fimaporfin (TPCS2a) is a photosensitiser drug being developed by PCI Biotech AS for use in novel Photochemical Internalisation (PCI) technology. PCI technology is designed to enhance the effects of other drugs in a site-specific, light-directed manner and is used to re-localise endocytosed molecules from endosomes to cytosol. This research study is evaluating the use of the PCI Technology in combination with adjuvant and vaccine antigens for safety and induction of immune responses.

开始日期2016-09-01

申办/合作机构

PCI Biotech AS

NCT01900158

/ Completed临床1期

A Phase I/II Dose Escalation Study to Assess the Safety, Tolerability and Efficacy of Amphinex®-Induced Photochemical Internalisation (PCI) of Gemcitabine in Patients With Advanced Inoperable Cholangiocarcinomas

This is a Phase I Dose Escalation Study in which the safety, tolerability and efficacy of Amphinex®--induced Photochemical Internalisation (PCI) of Gemcitabine followed by Gemcitabine/Cisplatin Chemotherapy will be assessed in patients with advanced inoperable cholangiocarcinomas.

开始日期2013-05-01

申办/合作机构

PCI Biotech AS

100 项与 Fimaporfin 相关的临床结果

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100 项与 Fimaporfin 相关的转化医学

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100 项与 Fimaporfin 相关的专利（医药）

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项与 Fimaporfin 相关的文献（医药）

2025-05-01·JOURNAL OF INVESTIGATIVE DERMATOLOGY

Inflammatory cutaneous reactions with systemic CD8+ T-cell responses upon photochemical internalization of antigens in mice

Article

作者: Hausammann, Lucy ; Halin, Cornelia ; Waeckerle-Men, Ying ; Fischer, Hendrik ; Duda, Agathe ; Sella, Federica ; Kolm-Djamei, Isabel ; Kündig, Thomas M ; Schineis, Philipp ; Haunerdinger, Veronika ; Johansen, Pål ; Li, Nick ; Kotkowska, Zuzanna K ; Høgset, Anders ; Selbo, Pål Kristian

Vaccination can prevent infections and modulate immune-related diseases. While conventional vaccines primarily stimulate CD4⁺ T cells and antibody production, effective anti-tumor immunity requires activation of CD8⁺ T cells. Photochemical internalization (PCI) is a promising technology that can facilitate cytosolic antigen delivery, promoting CD8⁺ T-cell responses. Here, we studied early immune and cutaneous reactions following PCI-based vaccination with the photosensitizer disulphonated tetraphenyl chlorine (TPCS2a). Mice were vaccinated intradermally with ovalbumin antigen and TPCS2a, followed by light treatment. We assessed cutaneous inflammatory reactions through histology, immunohistochemistry, fluorescence microscopy, and real-time PCR. Systemic inflammatory and immune reactions were analyzed in blood, lymph nodes, and in spleen by flow cytometry, clinical chemistry and ELISA. TPCS2a was retained in cutaneous structures, accumulated in draining lymph nodes, and light activation triggered dose- and time-dependent cutaneous inflammatory reactions including infiltration of innate myeloid CD11b⁺ and GR1⁺ macrophages, cross-presenting dendritic cells and neutrophils, alongside enhanced local and systemic production of pro-inflammatory cytokines. High TPCS2a doses triggered severe cutaneous and systemic reactions, but PCI-treated skin showed a high degree of plasticity and healing. These mechanistic insights into local and systemic effects of PCI-based vaccination may contribute to translating PCI into clinical practice and wider application.

2022-11-01·Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

All-trans retinoic acid enhances the anti-tumour effects of fimaporfin-based photodynamic therapy

Article

作者: Wong, Judith Jing Wen ; Selbo, Pål Kristian ; Lorenz, Susanne

The vitamin A metabolite all-trans retinoic acid (ATRA; tretinoin) has anticancer potential. However, lack of clinical success has prevented its approval for solid tumours. Herein, we propose combining short-term low-dose ATRA with fimaporfin-based photodynamic therapy (ATRA+PDT) for the improved treatment of solid cancers. Compared to monotherapies, ATRA+PDT induced synergistic cytotoxic responses including promotion of apoptosis in colon and breast carcinoma cell lines. Neither enhanced activity of alkaline phosphatase (ALP) nor increased expression of CD133 was detected after ATRA treatment indicating that the improved therapeutic effect of ATRA+PDT is independent of the differentiation state of the cancer cells. In the human colorectal adenocarcinoma cell line HT-29, the effect of ATRA+PDT on gene expression was evaluated by RNA sequencing (RNA-seq). We identified 1129 differentially expressed genes (DEGs) after ATRA+PDT compared to PDT. Ingenuity Pathway Analysis (IPA) predicted the unfolded protein response (UPR), interferon (IFN) signaling and retinoic acid-mediated apoptosis signaling as strongly activated canonical pathways after ATRA+PDT compared to PDT. A validation of the RNA-sec data by RT-qPCR revealed that ATRA+PDT elevated mRNA expression of early growth response 1 (EGR1) and strongly the stress-induced activating transcription factor 3 (ATF3), of which was confirmed on the protein level. In addition, ATRA+PDT abolished mRNA expression of regenerating islet-derived protein 4 (REG4). During the first 20 days post-ATRA+PDT, we obtained significant anti-tumour responses in HT-29 xenografts, including complete responses in 2/5 mice. In conclusion, ATRA+PDT represent a novel combination therapy for solid tumours that should be further tested in immunocompetent preclinical models.

2022-06-08·The oncologist

Photochemical Internalization of Gemcitabine Is Safe and Effective in Locally Advanced Inoperable Cholangiocarcinoma

Article

作者: Kasper, Stefan ; Hoffmeister, Albrecht ; Høgset, Anders ; Dechêne, Alexander ; Jürgensen, Christian ; Schirra, Jörg ; Walday, Per ; Selbo, Pål k. ; Neu, Bruno ; Jakobs, Ralf ; Sturgess, Richard ; Palmer, Dan ; Trojan, Jörg ; Finnesand, Lena ; Olivecrona, Hans

Abstract:

Background:

Photochemical internalization (PCI) is a novel technology for light-induced enhancement of the local therapeutic effect of cancer drugs, utilizing a specially designed photosensitizing molecule (fimaporfin). The photosensitizing molecules are trapped in endosomes along with macromolecules or drugs. Photoactivation of fimaporfin disrupts the endosomal membranes so that drug molecules are released from endosomes inside cells and can reach their therapeutic target in the cell cytosol or nucleus. Compared with photodynamic therapy, the main cytotoxic effect with PCI is disruption of the endosomal membrane resulting in delivery of chemotherapy drug, and not to the photochemical reactions per se. In this study we investigated the effect of PCI with gemcitabine in patients with inoperable perihilar cholangiocarcinoma (CCA).

Methods:

The in vitro cytotoxic effect of PCI with gemcitabine was studied on two CCA-derived cell lines. In a fimaporfin dose-escalation phase I clinical study, we administered PCI with gemcitabine in patients with perihilar CCA (n = 16) to establish a safe and tolerable fimaporfin dose and to get early signals of efficacy. The patients enrolled in the study had tumors in which the whole length of the tumor could be illuminated from the inside of the bile duct, using an optical fiber inserted via an endoscope (Fig. 1). Fimaporfin was administered intravenously at day 0; gemcitabine (i.v.) and intraluminal biliary endoscopic laser light application on day 4; followed by standard gemcitabine/cisplatin chemotherapy.

Results:

Preclinical experiments showed that PCI enhanced the effect of gemcitabine. In patients with CCA, PCI with gemcitabine was well tolerated with no dose-limiting toxicities, and no unexpected safety signals. Disease control was achieved in 10 of 11 evaluable patients, with a clearly superior effect in the two highest dose groups. The objective response rate (ORR) was 42%, including two complete responses, while ORR at the highest dose was 60%. Progression-free survival at 6 months was 75%, and median overall survival (mOS) was 15.4 months, with 22.8 months at the highest fimaporfin dose.

Conclusion:

Photochemical internalization with gemcitabine was found to be safe and resulted in encouraging response and survival rates in patients with unresectable perihilar CCA.

项与 Fimaporfin 相关的新闻（医药）

2023-09-22

·生物制品圈

解决内体逃逸，基于光化学内化技术递送RNA分子，挪威PCI Biotech的fimaNAc递送技术将获得欧洲专利局授权

近日，挪威生物制药公司PCI Biotech（OSE：PCIB）宣布，欧洲专利局（EPO）已通知他们，计划为其用于递送mRNA分子的fimaNAc技术授予一项新专利，该技术预计将主要应用于皮肤病学领域。欧洲专利的保护期至2039年，该专利申请正在美国和主要亚洲市场等待批准。PCI Biotech是一家专注于通过其创新的光化学内化（PCI）技术平台开发和商业化新疗法和新技术的公司，为了更清晰地介绍该公司的技术平台，本文将分为以下几个方面：内体逃逸：药物研发中的关键挑战光化学内化（PCI）技术fimaNAc平台fimaVACC平台内体逃逸在药物研发中的挑战在细胞生物学中，内体是一种小囊泡，它通过细胞膜的内吞过程形成，用于捕获并运输细胞外的物质。当药物被细胞摄取时，它们经常被包裹在这些内体中。然而，要使药物在细胞内发挥作用，它们必须从内体中“逃逸”到细胞质或其他细胞器中。为什么内体逃逸是一个挑战？囊化的药物：许多药物，特别是大分子药物如核酸或蛋白质，不能直接穿越细胞膜。因此，它们通过受体介导的内吞被摄取到细胞内，并被囊化在内体中。溶酶体降解：如果药物不能及时从内体中逃逸，内体可能会与溶酶体融合。溶酶体含有能够分解许多生物分子的酶，这可能导致药物被降解，从而失去其治疗效果。逃逸效率：即使某些药物能够从内体中逃逸，其逃逸效率也可能不高，这意味着只有一小部分药物能够到达其细胞内的目标位置。药物研发中的应对策略为了解决内体逃逸的问题，科学家们已经开发了多种策略：使用递送载体：例如脂质体或纳米颗粒，这些载体可以帮助药物从内体中逃逸。pH敏感材料：这些材料在酸性的内体环境中会发生结构或化学变化，从而导致内体膜的破裂和内容物的释放。病毒融合肽：某些病毒（如流感病毒）具有能够与内体膜融合的特定蛋白片段，从而释放其基因物质到细胞质中。离子通道形成剂：某些化合物可以在内体膜上形成离子通道，导致膜的去稳定化和内容物的释放。光化学内化：这是一种使用光来触发内体逃逸的策略，如PCI Biotech所使用的技术。总之，内体逃逸是药物研发中的一个重要挑战，但通过创新的策略和技术，科学家们正在努力克服这一挑战，以开发更有效的治疗方法。光化学内化（PCI）技术PCI Biotech的光化学内化（photochemical internalisation，PCI）技术，使用了一个关键的光敏分子Fimaporfin (TPCS2a），一种定位在内体/溶酶体的光敏剂。以Fimaporfin构建的载体，当药物被内吞进入内体时，便可以通过光控，来激活并诱导光引发的内体释放（ light-triggered endosomal release），保证药物完美克服因内体逃逸困难所导致的低效问题。另外，不同的波长还将导致不同的组织渗透。fimaNAc平台本次申请专利的fimaNAc技术，是一种核酸递送技术，既适用于mRNA也适用于siRNA。根据最新的年报，公司计划将该技术应用于两方面，皮肤病的治疗和生物工艺（Bioprocessing ）。内体逃逸也是核酸药物递送的核心挑战之一。具体而言，mRNA药物进入体内需要经历一段漫长的旅程，mRNA-LNP首先通过静电相互作用吸附在细胞膜表面，经胞吞进入细胞内的“内体”，在内体中，mRNA-LNP将被脂肪泡和内体壁两层膜包裹，如果要顺利进入细胞质完成mRNA翻译，内体逃逸将是mRNA-LNP最关键的步骤。如果没有及时逃逸，内体成熟后便会和溶酶体相融合，LNP和包裹其中的mRNA分子则将被溶酶体内的酸性环境和水解酶降解。因此，在皮肤病方向，PCI+mRNA将具有以下优势：局部治疗: 光化学内化（PCI）是一种非常定位的治疗方法，只在应用光线的地方发生作用。这使得它特别适用于皮肤病，因为皮肤是容易接触和照射的。高效递送:fimaNAC技术能有效地实现内体逃逸，将mRNA分子递送到细胞内，从而提高治疗效果。减少副作用: 由于PCI技术是局部应用的，因此可能会减少全身性副作用，这是许多其他治疗方法（如口服或注射药物）可能带来的问题。从该公司披露的数据，在小鼠实验中，可见，fimaNAC技术递送的mRNA分子，其表达效率远高于LNP，且具有高度靶向性。fimaVACC平台fimaVacc计划旨在通过触发抗原或编码抗原的核酸或免疫刺激因子的内体释放来增强癌症的免疫治疗。在这部分介绍中，公司年报中的图示相对清晰，这里直接截取概括性图示，以来说明PIC技术在肿瘤治疗中的应用：应用一：MoA应用二:冷肿瘤转向热肿瘤参考资料https://static1.squarespace.com/static/5e8741643c3bbc6a64cd0b0f/t/644b7dcade3f79140101688e/1682669005980/2022+Annual+report+PCI+Biotech+Holding+ASA.pdfhttps://ml-eu.globenewswire.com/Resource/Download/741738a4-bc6b-40a4-8f27-4810ba2942c1https://ml-eu.globenewswire.com/Resource/Download/265ca07a-cab4-459d-8ba3-5a3aea56de4a为促进抗体行业的交流与创新，2023年10月14-15日第六届金秋十月抗体产业发展大会如约而至。会议旨在为研究人员提供一个互动交流的平台，有助于推动抗体产业的进一步发展。会议内容时间：2023年10月14-15日地点：苏州（酒店定向通知）规模：600-800人主办单位：生物制品圈、抗体圈指导单位：康维讯生物、夏尔巴生物会议费用：免费FREE!（仅收取50元报名定金，含参会学习、茶歇、会议手册，定金概不退还），9月15日报名定金提高到100元，先到先得，报完即止，超过9月20日预登记将收取会议费！报名方式：扫描下方二维码或点击文章最底部“阅读原文”→ 填写表格 → 报名成功（报名志愿者，承担一定工作，请慎重考虑，免交定金）！组委会获得报名信息后，根据报名信息进行初筛，并进一步与报名者沟通确认，实现精准邀请。最终有机会进入大会微信群（严格审核通过）。日程安排更多嘉宾仍在邀请中。。。。。。识别微信二维码，添加生物制品圈小编，符合条件者即可加入生物制品微信群！请注明：姓名+研究方向！版权声明本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

信使RNA

2011-06-24

·BioSpace

PCI Biotech: Main Results of the Full Phase I/II study of Amphinex(R)

OSLO, Norway--(BUSINESS WIRE)--PCI Biotech (PCIB) the Norwegian biopharmaceutical company, reported today the main results of the completed Phase I/II study of the new component Amphinex® in the combination productPC-A11, where Amphinex is used in combination with the cytotoxic agent bleomycin. The primary objective of this dose escalation study is to assess the maximum tolerated dose of the new component Amphinex®. Secondary objectives include determination of the antitumour effect of the PC-A11 treatment, as well as pharmacokinetics of the Amphinex® component.

100 项与 Fimaporfin 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
复发性头颈癌	临床2期	法国	PCI Biotech AS	2012-04-01
复发性头颈癌	临床2期	德国	PCI Biotech AS	2012-04-01
复发性头颈癌	临床2期	立陶宛	PCI Biotech AS	2012-04-01
复发性头颈癌	临床2期	荷兰	PCI Biotech AS	2012-04-01
复发性头颈癌	临床2期	波兰	PCI Biotech AS	2012-04-01
复发性头颈癌	临床2期	英国	PCI Biotech AS	2012-04-01
头颈部鳞状细胞癌	临床2期	法国	PCI Biotech AS	2012-04-01
头颈部鳞状细胞癌	临床2期	德国	PCI Biotech AS	2012-04-01
头颈部鳞状细胞癌	临床2期	立陶宛	PCI Biotech AS	2012-04-01
头颈部鳞状细胞癌	临床2期	荷兰	PCI Biotech AS	2012-04-01

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临床结果

适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04099888 (RELEASE, CTgov)	临床2期	肝外胆管癌	41	Fimaporfin+Gemcitabine+gemcitabine+cisplatin (PCI Treatment in Conjunction With Standard of Care (SoC))	窪選網膚願鹽獵繭衊鏇(鬱鹹顧鑰淵獵鹹簾衊鏇) = 廠築顧蓋艱繭鏇鹹網衊觸積憲顧鬱積製鹹繭餘 (襯簾網憲窪窪製襯鑰壓, 願遞鹽淵獵繭齋鬱鏇範 ~ 壓醖觸網糧積廠範糧餘) 更多	-	2023-09-11
NCT04099888 (RELEASE, CTgov)	临床2期	肝外胆管癌	41	gemcitabine+cisplatin (Standard of Care (SoC))	窪選網膚願鹽獵繭衊鏇(鬱鹹顧鑰淵獵鹹簾衊鏇) = 簾淵窪壓蓋淵顧積齋範觸積憲顧鬱積製鹹繭餘 (襯簾網憲窪窪製襯鑰壓, 夢衊鏇憲夢餘鹹遞獵憲 ~ 膚鹽餘廠壓蓋鏇糧鹽選) 更多	-	2023-09-11
NCT01900158 (ESMO2018) 人工标引	临床1期	克拉茨金瘤	16	Cisplatin+Fimaporfin+gemcitabine	網觸製夢廠醖餘簾簾膚(餘範衊蓋範築壓蓋範鏇) = 簾願網繭壓壓繭獵襯鏇蓋鹹願衊遞鹽蓋膚築積 (積鹽遞繭鑰構齋壓餘願 ) 更多	积极	2018-10-21