Immunization Using Polysialic Acid-KLH or N-Propionylated Polysialic Acid-KLH Conjugate Plus the Immunological Adjuvant QS-21 in Patients With Small Cell Lung Cancer Who Have Achieved a Major Response to Initial Therapy

RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Biological therapies, such as QS21, use different ways to stimulate the immune system and stop cancer cells from growing.
PURPOSE: Phase II trial to study the effectiveness of vaccine therapy plus QS21 in treating patients who have small cell lung cancer that has responded to initial therapy.

开始日期1998-08-01

申办/合作机构

Memorial Sloan Kettering Cancer Center

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100 项与 Insulin polysialic(Lipoxen Technologies Ltd.) 相关的转化医学

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100 项与 Insulin polysialic(Lipoxen Technologies Ltd.) 相关的专利（医药）

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项与 Insulin polysialic(Lipoxen Technologies Ltd.) 相关的文献（医药）

2021-03-15·Angewandte Chemie International Edition

A Macromolecular Drug for Cancer Therapy via Extracellular Calcification

Article

作者: Li, Hanhui ; Feng, Shuaishuai ; Chen, Yanni ; Wang, Ben ; Zhang, Xueyun ; Chen, Xinhua ; Tang, Ning ; Shou, Hao ; Zhang, Lihong ; Luo, Yan ; Tang, Ruikang

AbstractCancer chemotherapy typically relies on drug endocytosis and inhibits tumor cell proliferation via intracellular pathways; however, severe side effects may arise. In this study, we performed a first attempt to develop macromolecular‐induced extracellular chemotherapy involving biomineralization by absorbing calcium from the blood through a new type of drug, polysialic acid conjugated with folate (folate‐polySia), which selectively induces biogenic mineral formation on tumor cells and results in the pathological calcification of tumors. The macromolecule‐initiated extracellular calcification causes cancer cell death mainly by intervening with the glycolysis process in cancer cells. Systemic administration of folate‐polySia inhibited cervical and breast tumor growth and dramatically improved survival rates in mice. This study provides an extracellular therapeutic approach for malignant tumor diseases via calcification that is ready for clinical trials and offers new insights into macromolecular anticancer drug discovery.

2020-03-01·European Journal of Pharmaceutical Sciences2区 · 医学

Development of a nattokinase–polysialic acid complex for advanced tumor treatment

2区 · 医学

Article

作者: Wang, Siyu ; Chen, Jiepeng ; Kou, Yanmei ; Feng, Rui ; Wang, Tianyue ; Song, Yanzhi ; Hu, Yawei ; Zhang, Ning ; Duan, Lili ; Deng, Yihui

Cancer-associated thrombus (CAT) impedes delivery of nanoparticles to tumor sites and also inhibits the ability of immune cells to detect and attack these tumors, particularly in advanced tumors with old thrombi. Nattokinase (NK) is an extract from a popular Japanese food, natto, which consists of boiled soybeans fermented with bacteria. Nattokinase exerts strong fibrinolytic and thrombolytic activities and can unblock blood vessels. To deliver NK to thrombus sites in tumors, we modified the surface of NK with polysialic acid (PSA), which formed complexes via electrostatic interactions, resulting in NK-PSA. Particle size and zeta potential of NK-PSA were evaluated, and differential scanning calorimetry, Fourier-transform infrared spectroscopy, and morphological analyses of NK-PSA were performed. To determine the efficacy of the NK-PSA complex on delivery of nanoparticulate drugs, sialic acid-modified doxorubicin liposomes (DOX-SAL) were used as a model drug. In vivo pharmacokinetic and tissue distribution analyses showed that the blood clearance rate of DOX-SAL was significantly enhanced by NK-PSA, and NK-PSA increased accumulation of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide (DiR) labeled SAL (DiR-SAL) in tumors. Analysis of anti-tumor efficacy showed that the combination of NK-PSA and DOX-SAL enhanced anti-tumor activity. These results suggested that NK-PSA combined with DOX-SAL may be an effective strategy to clear CAT and increase the ability of nanoparticles and immune cells to reach tumors.

2018-03-01·Biotechnology Reports

Single-use membrane adsorbers for endotoxin removal and purification of endogenous polysialic acid from Escherichia coli K1

Article

作者: de Vries, Ingo ; Hellmann, Zawadi ; Kopatz, Jens ; Beutel, Sascha ; Neumann, Harald ; Schreiber, Sarah ; Boßmann, Daniel

Polysialic acid (polySia) is a promising molecule for various medical applications (e.g., treatment of inflammatory neurodegenerative diseases). In this study a complete production process for human-identical α-(2,8)-linked polySia was developed using a disposable bioreactor for cultivation of Escherichia coli K1 and single-use membrane adsorbers for downstream processing (DSP). The cultivation process was optimized to minimize complex media components and a maturation process after cultivation was established. The maturation led to further product release from the cell surface into the supernatant. Afterwards DSP was established using sodium hydroxide treatment combined with anion exchange membrane adsorbers for endotoxin and DNA depletion. After downstream processing the final product had neither detectable protein nor DNA contamination. Endotoxin content was below 3 EU mg^-1. Investigation of the maximal chain length showed no effect of the harsh sodium hydroxide treatment during DSP on the stability of the polySia. Maximal chain length was ∼98 degree of polymerization.

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
中枢神经系统疾病	临床1期	-	SynBio LLC	-
中枢神经系统疾病	临床1期	-	Xenetic Biosciences, Inc.	-
1型糖尿病	临床1期	-	Xenetic Biosciences, Inc.	-
1型糖尿病	临床1期	-	SynBio LLC	-
2型糖尿病	临床1期	-	Xenetic Biosciences, Inc.	-
2型糖尿病	临床1期	-	SynBio LLC	-