Polyclonal antibody stimulator(Aphton Corp.)(Polyclonal antibody stimulator(Aphton Corp.))

概要

基本信息

药物类型

治疗性疫苗、结合疫苗

别名

Anti-gastrin 17 immunogen、Antigastrin 17、Gastrimmune

+ [9]

靶点

GAST

作用方式

抑制剂、刺激剂

作用机制

GAST抑制剂(促胃泌素17抑制剂)、免疫刺激剂

治疗领域

肿瘤消化系统疾病内分泌与代谢疾病+ [2]

在研适应症-

非在研适应症

大肠腺癌晚期结直肠腺癌食管癌+ [5]

原研机构

Aphton Corp.

在研机构-

非在研机构

Cancer Advances, Inc.

权益机构-

最高研发阶段终止临床3期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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关联

16

项与 Polyclonal antibody stimulator(Aphton Corp.) 相关的临床试验

NCT00020787

/ Completed临床3期IIT

An Open Label, Sequential Multi-Center Multi Dose Study Of G17T Immunogen In Combination With Cisplatin (CDDP) And 5-Fluorouracil (5-FU) In Subjects With Metastatic Or Locally Recurrent Gastric Or Gastroesophageal Cancer Previously Untreated With Chemotherapy For Advanced Disease (Stage IV)

RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining vaccine therapy with chemotherapy may kill more tumor cells.
PURPOSE: Phase II trial to study the effectiveness of combining vaccine therapy and chemotherapy in treating patients who have metastatic or locally recurrent stomach cancer or esophageal cancer.

开始日期2001-07-01

申办/合作机构

Jonsson Comprehensive Cancer Center

NCT02118077

/ Completed临床3期

A Prospective, Randomized, Double-blind, Placebo-controlled, Group Sequential Trial of G17DT for the Treatment of Advanced Pancreatic Cancer.

Compare the effect of G17DT with that of placebo on the survival of subjects with advanced pancreatic cancer.

开始日期2001-04-01

申办/合作机构

Cancer Advances, Inc.

NCT02118064

/ Completed临床2期

A Multinational, Multicenter, Open-label, Single-arm, Phase II Study of G17DT Immunogen in Combination With Irinotecan in Metastatic Colorectal Carcinoma Refractory to Previous Irinotecan-based Chemotherapy.

This study was designed to evaluate the ability for G17DT to slow or arrest tumor growth in patients with refractory colon cancer who had been previously treated with an Irinotecan-based chemotherapy.

开始日期2001-03-01

申办/合作机构

Cancer Advances, Inc.

100 项与 Polyclonal antibody stimulator(Aphton Corp.) 相关的临床结果

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100 项与 Polyclonal antibody stimulator(Aphton Corp.) 相关的转化医学

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100 项与 Polyclonal antibody stimulator(Aphton Corp.) 相关的专利（医药）

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2,520

项与 Polyclonal antibody stimulator(Aphton Corp.) 相关的文献（医药）

2026-03-01·JOURNAL OF PLANT PHYSIOLOGY

The mechanisms by which polyamines regulate wheat grain filling under drought stress conditions

Article

作者: Afjeh, Sara Sadat ; Ahmadi, Ali ; Abbasi, Ali Reza ; Mostafaie, Pouria

Drought stress (DS) is a major factor limiting wheat grain filling. Polyamines (PAs) play crucial roles in plant responses to DS; however, the mechanisms underlying their effects on grain filling are not fully understood. This study aimed to clarify the regulatory role of PAs in grain filling through source-sink dynamics in two wheat cultivars representing distinct drought tolerance under non-stress and DS conditions, with or without exogenous spermine and putrescine. Data indicated that DS significantly disrupted the grain-filling process (P < 0.01), accompanied by severe limitations in source-sink capacity. However, PA application improved chlorophyll content (9.45-23.39 %), Fv/Fm values (1.86-5.56 %), assimilate partitioning to non-structural carbohydrates (4.24-7.17 %), and stem reserves (6.42-24.44 %), thereby enhancing source capacity. PAs also reduced abscisic acid (ABA) levels during early grain-filling stages and increased auxin and cytokinin levels, which were associated with enhanced endosperm cell division and number (P < 0.05), thereby improving sink capacity. In later grain-filling stages, PAs caused a controlled increase in ABA levels, serving as physiological signals for reserve mobilization and significantly inducing the expression of 1-FEH-w3 and SPSI genes (P < 0.01). These changes were accompanied by improved stem reserve remobilization (RM) (6-16.70 %), grain-filling rate, and grain yield (P < 0.05). The cultivars' responses to spermine application were more evident than to putrescine, particularly in the sensitive cultivar. Overall, PAs could significantly enhance grain filling and sustain wheat yield under DS conditions, likely through a multifaceted mechanism involving hormonal regulation, maintaining source-sink capacity, and facilitating RM.

2026-03-01·PHYTOMEDICINE

Hemoglobin adduction and impaired oxygen transport define the etiology of pyrrolizidine alkaloid-induced pulmonary arterial hypertension

Article

作者: He, Yisheng ; Song, Zijing ; Guo, Xiaokai ; Huang, Tianyang ; Fan, Yujian ; Zhang, Caibin ; Ma, Jiang

BACKGROUND:

Pyrrolizidine alkaloids (PAs), particularly monocrotaline (MCT), are common phytotoxins known to induce pulmonary arterial hypertension (PAH), a progressive and fatal cardiopulmonary disease. However, the specific mechanism initiating PAH and the basis for the differing toxic potencies among PAs, such as MCT and retrorsine (RTS), remain undefined.

PURPOSE:

This study aimed to investigate the mechanistic basis for the marked difference in pulmonary toxicity between two representative PAs, MCT and RTS. We specifically tested the hypothesis that the severity of PA-induced lung injury is determined by the extent of hemoglobin adduction within red blood cells (RBCs) and the consequent impairment of oxygen transport.

STUDY DESIGN:

We employed a comparative toxicological design using rat models, treating them with equimolar doses of MCT and RTS, to assess and compare their respective toxicological pathways and resulting pulmonary injury.

METHODS:

Rats were administered MCT or RTS. Dehydropyrrolizidine alkaloid (DHPA) adduct formation on RBC hemoglobin was profiled using proteomics. Pulmonary hemodynamics, pulmonary vascular remodeling, and systemic hypoxia levels were subsequently measured.

RESULTS:

DHPAs selectively and covalently bound to specific residues (D74, E91, H93, K133) on the hemoglobin β-1 chain, critically impairing the oxygen-carrying capacity of RBCs. MCT exposure resulted in significantly higher levels of pyrrole-hemoglobin adducts (approximately 95% binding) compared to RTS (approximately 70% binding). This higher adduction rate led to more severe systemic hypoxia, which was consistently associated with greater pulmonary arterial endothelial activation and more severe PAH in the MCT group.

CONCLUSION:

The severity of PA-induced PAH is directly correlated with the degree of hemoglobin adduction and resulting hypoxia. Hemoglobin adduction and impaired oxygen transport are critical, upstream events that define the etiology of PA-induced pulmonary arterial hypertension.

2026-02-12·JOURNAL OF MEDICINAL CHEMISTRY

Short-Chain and Long-Chain Fatty Acid-Containing Platinum–Acridine Anticancer Prodrugs: Exploiting Alternative Mechanisms of Cellular Internalization

Article

作者: Wolf, Lilly ; Fontoura, Beatriz M. ; Halatek, David J. ; Feder, Samuel M. ; Jones, Bradley T. ; Sapp, Lauren A. ; Bierbach, Ulrich ; Bo, Sarah A. ; Marrs, Glen S. ; Coffin, Dylan J.

Platinum-acridine hybrid agents (PAs) represent a mechanistically unique class of DNA-targeted anticancer compounds with superior potency compared to cisplatin, but systemic toxicity has limited their clinical utility. To address this, we have developed platinum(IV) prodrugs of PAs for controlled reductive activation in tumor tissues. Short-chain fatty acid (SCFA) containing derivatives demonstrated nanomolar cytotoxicity in cancer cells expressing human multidrug and toxin extrusion protein 1 (hMATE1), consistent with rapid transporter-dependent uptake. Long-chain fatty acid (LCFA)-modified derivatives were less potent than the SCFA-based prodrugs in hMATE1^high NCI-H460 (lung) and HepG2 (liver) cancer cells. Conversely, the LCFA derivatives, which target human serum albumin (HSA) and utilize the blood protein for cellular entry, showed an order of magnitude higher activity than the SCFA derivatives in hMATE1^low HCT116 colon cancer cells. Together, these prodrug strategies hold promise of extending treatment with PAs to hMATE1-deficient cancers and improving the therapeutic window of the hybrid agents.

1

项与 Polyclonal antibody stimulator(Aphton Corp.) 相关的新闻（医药）

2023-02-28

·BioSpace

Cancer Advances, Inc. Announces Issuance of New U.S. Patent - February 28, 2023

DURHAM, N.C., Feb. 28, 2023 (GLOBE NEWSWIRE) -- Cancer Advances, Inc., a clinical stage biopharmaceutical company developing therapeutics for gastrointestinal (GI) cancers, announced that the U.S. Patent and Trademark Office has issued new patent No. 11,583,576, enhancing the Company’s intellectual property position for lead asset Polyclonal Antibody Stimulator (PAS) vaccine. The new patent titled “Compositions and Methods for Inducing Humoral and Cellular Immunities against Tumors and Cancer” covers a method for treating and/or preventing and/or inhibiting development of a tumor and/or a cancer associated with gastrin signaling in a subject. Gastrin mediated tumors include, but are not limited to, gastrointestinal cancers. The novel IP further covers methods for treatment of GI cancer by administering PAS followed by an immune checkpoint inhibitor. A related claim covers reduction in fibrosis associated with pancreatic cancer via the administration of this combination. “After more than six years of research, we are excited to have this patent issued. We have known that PAS can induce the development of antibodies to Gastrin, bringing Gastrin levels down and increasing survival times by 50% in GI clinical trials. With our research now demonstrating that PAS is able to alter the tumor microenvironment, it opens the door to many new opportunities to improve current treatment for GI cancer patients,” commented Lynda Sutton, President of Cancer Advances. The issued patent adds to the over one hundred granted global patents for PAS. Cancer Advances plans to seek approval for PAS in the treatment of gastric and pancreatic cancers. About Cancer Advances, Inc. Cancer Advances Inc. (Durham, NC) is a biotechnology company focused on impacting human health and preventing the progression of gastrointestinal cancers by enhancing the adaptive immune system. The company is led by an experienced management team with over one hundred and twenty years of combined experience in drug development and commercialization experience. About Polyclonal Antibody Stimulator (PAS) Polyclonal Antibody Stimulator (PAS) vaccine is an immunomodulator potentially applicable in multiple cancer types including gastric, pancreatic, and colorectal. The vaccine is a peptide-conjugate that includes an N-terminal epitope of human gastrin-17 (G17) linked to carrier diphtheria toxoid. PAS has been studied in multiple clinical trials, in over 1,500 human subjects, and has demonstrated an excellent safety and tolerability profile. Cancer Advances exclusively owns PAS and is funding and managing all aspects of the PAS gastrin vaccine program. Contact Cancer Advances, Inc. E-mail: jwingen@canceradvances.com

疫苗免疫疗法

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB04914

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
胰腺腺癌	临床3期	-	Cancer Advances, Inc.	2000-08-14
食管癌	临床2期	-	Cancer Advances, Inc.	2000-08-01
胃食管交界处恶性肿瘤	临床2期	-	Cancer Advances, Inc.	2000-08-01
胃癌	临床2期	英国	Cancer Advances, Inc.	2000-02-01
胃腺癌	临床2期	-	Cancer Advances, Inc.	1998-09-01
转移性结直肠癌	临床2期	-	Cancer Advances, Inc.	1994-05-01
大肠腺癌	临床2期	英国	Cancer Advances, Inc.	1993-10-01
晚期结直肠腺癌	临床2期	英国	Cancer Advances, Inc.	1993-10-01

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临床结果

适应症

分期

评价

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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


ASCO2006	临床3期	-	-	Gemcitabine + G17DT	網構網糧繭餘繭簾選醖(鬱齋鬱鏇遞鑰鹹鹹糧艱) = 築襯膚鹹顧餘醖觸觸糧簾鬱夢簾範鏇餘鹹齋齋 (願構顧簾繭構遞鑰顧選 )	-	2006-06-20
				Gemcitabine alone (placebo)	網構網糧繭餘繭簾選醖(鬱齋鬱鏇遞鑰鹹鹹糧艱) = 夢蓋憲夢製顧鹽鏇夢蓋簾鬱夢簾範鏇餘鹹齋齋 (願構顧簾繭構遞鑰顧選 )
ASCO2004	N/A	晚期胰腺腺癌	154	G17DT	顧遞鏇蓋範選糧壓鹽齋(餘積膚鬱鏇選積觸簾衊) = 鏇淵願選顧繭簾鹹膚鏇襯選蓋構膚齋餘選鹹繭 (鏇襯遞鑰艱範醖選淵鏇 )	积极	2004-07-15
				Placebo	顧遞鏇蓋範選糧壓鹽齋(餘積膚鬱鏇選積觸簾衊) = 夢選鑰憲餘壓窪夢簾製襯選蓋構膚齋餘選鹹繭 (鏇襯遞鑰艱範醖選淵鏇 )