Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Combination treatment of pancreatic cancer

Inactive Publication Date: 2006-06-29
CANCER ADVANCES INC
View PDF37 Cites 18 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0036] Contrary to expectations, it has now been discovered that the immune response to vaccination of the treated animal

Problems solved by technology

Therefore, antagonism of CCK-B receptors may not be the optimal method to suppress the proliferative action of gastrin present either in the serum or produced locally by the tumor cells.
However, these antagonists have severe toxic side effects and lack specificity as they block the action of all potential ligands of the receptor such as G34 and CCK in normal cells.
The main problem with these compounds is their lack of potency, with relatively high concentrations required to displace G17.
Due to the low specificity of this class of gastrin antagonising agents for the gastrin / CCKB receptor, the inhibition of tumor growth may not be effectively control with gastrin antagonists.
Thus, if complete inhibition of gastrin binding to the receptor does not occur in the autocrine growth cascade, then the gastrin antagonists may be unable to block this mechanism of tumor growth promotion.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Examples

Experimental program
Comparison scheme
Effect test

example a

[0078] G17DT was administered to 28 patients with advanced pancreatic adenocarcinoma at weeks 0,1 and 3 at a 250 μg dose[16]. Only one patient failed to mount an antibody response. G17DT was well tolerated with no systemic side effects. One patient developed a sterile abscess that settled following aspiration. Survival was found to be significantly improved in G17DT patients when compared to an historical control matched in terms of age, stage and co-existing morbidity by POSSUM scoring[40].

[0079] Concerning the response rates of subjects with pancreatic cancer the median time to onset of the immune response to G17DT appears to be dose related and to be optimal at ≧250 μg G17DT.

example b

[0080] The immuno-electronmicroscopy studies used an antiserum directed against the amino-terminal end of the CCK-B / gastrin-receptor (GRE-1 epitope) show that after one hour incubation, the distribution of immunogold-label CCK-B / gastrin-receptor antibody was quickly internalized as 12% of the antibody receptor complex was associated with the cell membrane, 36.6% within the cytoplasm, 7.9% in the nuclear membrane and, quite surprisingly, 43.5% within the cell nucleus. Areas of intense CCK- B / gastrin-receptor immunoreactivity within the nucleus were found on chromatin, which may suggest specific binding sites for regulation of the DNA.

[0081] These electron microscopy studies with anti-immunoglobulin conjugated to gold beads (immmunogold) reveal that an extremely rapid turnover of the anti-receptor / receptor complex occurs in the tumor cells; as early as 10 seconds after exposure to antibodies, complexes are detectable in the cell nucleus.

example c

Immunological Efficacy

[0082] Patients' sera were assessed for antibodies to G17 gastrin at 2-4 weekly intervals. Anti-gastrin-17 antibodies were measured using a titration and inhibition radioimmunoassay with 125I labeled human gastrin-17. Assays for antibodies to G17 gastrin in the pancreatic cancer trials 1 and 2 have been performed by a G17 antigen-based ELISA.

[0083] The pharmacodynamics of the immune response to G17DT was evaluated as a function of the dose and treatment regimen for G17DT. The frequency of seroconversion and time to onset of production of G17 gastrin-specific antibodies was used to estimate the optimal dose.

[0084] A positive immune response in test serum by RIA was defined as being ≧40 fold above non-specific background determined on a 1:40 dilution of pre-immune subject serum within the first 12 weeks post-immunization. This corresponds to approximately 10% of total 125I G17 cpm added in the RIA assay. A positive response in the ELISA assay approximates ≧4 u...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
Massaaaaaaaaaa
Massaaaaaaaaaa
Massaaaaaaaaaa
Login to View More

Abstract

A combination for use in the treatment of pancreatic cancer comprising: (i) an anti-gastrin effective immunogenic composition; and, (ii) one or more chemotherapeutic agents suitable for inhibiting cancer growth.

Description

[0001] This application claims the benefit of U.S. provisional patent application 60 / 278,294 filed Mar. 23, 2001.FIELD OF THE INVENTION [0002] The invention relates to a combination of immunological and chemotherapeutic treatment of pancreatic cancer. In particular, treatment of locally advanced or metastatic gastrin-dependent pancreatic adenocarcinoma in the form of immunization is provided against gastrin hormone in combination with one or more anti-cancer drugs. BACKGROUND OF THE INVENTION [0003] In 1998, approximately 29,000 people in the United States were diagnosed with pancreatic adenocarcinoma, and approximately 28,900 people were expected to die from this tumor[1]. The overall cure rate for pancreatic cancer remains less than 5% despite more than 20 years of clinical trials. Only 10% of subjects have a potentially resectable tumor; however, even for subjects undergoing a curative pancreaticoduodenectomy, five-year survival is 6-24%[2]. The vast majority of subjects have unr...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): A61K39/395A61K31/4745A61K9/107A61K31/7068A61K33/24A61K39/00A61K45/00A61P35/00A61P43/00C07K16/26
CPCA61K39/0005A61K39/0011A61K2039/505A61K2039/6037C07K16/26A61P35/00A61P35/04A61P43/00A61K39/00113A61K39/001103
Inventor GEVAS, PHILIPMICHAELI, DOVGRIMES, STEPHENCAPLIN, MARTYN
Owner CANCER ADVANCES INC
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com