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

Method for upregulating antigen expression

Inactive Publication Date: 2016-04-14
NORDIC NANOVECTOR
View PDF4 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent describes a way to treat tumors using radioimmunotherapy. In this method, a low dose of treatment is given that has a low effect on killing tumor cells, but it does increase the expression of antigens. This can help to make the tumor easier to treat with other methods, like chemotherapy or immunotherapy.

Problems solved by technology

However it was not known if low doserate radioimmunotherapy could upregulate antigen expression.
A problem with this approach is that experimental work and clinical data have indicated that antibody therapy can cause antigen drift that is a selection pressure towards cells with low antigen expression, which become treatment resistant (Musto and D'Auria, 2011).

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

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Method for upregulating antigen expression
  • Method for upregulating antigen expression
  • Method for upregulating antigen expression

Examples

Experimental program
Comparison scheme
Effect test

example 1

Treatment with Betalutin (177Lu-tetraxetan-tetulomab, or 177Lu-HH1) and Effect on Antigen Expression

[0182]Materials & Methods:

[0183]Labelling of Antibodies

[0184]Labelling of the antibody HH-1 with p-SCN-Bn-DOTA and 177Lu was performed following standard procedures described in Dahle et al. (2013) and Repetto-Llamazares et al. (2013). The radiochemical purity (RCP) of the radioimmunoconjugate (RIC) was evaluated using Instant Thin Layer Chromatography. If RCP was below 95% the conjugate was purified using Econo-Pac 10 DG columns (Bio-rad Laboratories, California, USA). RCP was higher than 97% for all RICs used in the experiments. The specific activity of Betalutin was 92 MBq / kg with an antibody concentration of 178 μg / ml. The immunoreactive fractions (IRFs) of the RICs were estimated using Ramos and Daudi lymphoma cells and a one point assay. A cell concentration of 75 million cells / ml were used. Cells incubated with cold tetulomab were used to assess the non-specific binding. Blocke...

example 2

Introduction

[0194]To evaluate if the effect from 177Lu-tetulomab was due to cell specific radiation, Daudi cells were incubated with Betalutin for 1 h.

[0195]Materials and Methods

[0196]Labelling of Antibodies

[0197]The procedure used to label the antibodies and to calculate the IRF has been previously discussed in Example 1. The specific activity of 177Lu-tetulomab was 212 MBq / mg and the Ab concentration was 0.5 mg / ml. The IRF was 72+ / −2% and it was measured in Ramos cells.

[0198]Treatment of Cells

[0199]The procedure followed to treat the cells was similar to the one described in example 1. Two different treatments were evaluated in this example. One treatment involved incubation of cells during 24 hours, similarly to what was done in example 1. The other treatment involved incubation of cells during 1 hour. Control cells were prepared for each of the treatments as described in example 1. The same amount of activity was added to both treatments (4.6 MBq, the same activity as given in e...

example 3

Introduction

[0204]To study if the upregulation of antigens was a general feature of lymphoma rather than a cell line specific effect, Daudi cells were tested together with the three other lymphoma cells lines, Raji, Ramos and Rec-1.

[0205]Materials and Methods

[0206]Labelling of Antibodies

[0207]The procedure used to label the antibodies and to calculate the IRF has been previously discussed in Example 1. The specific activity of 177Lu-tetulomab was 212 MBq / mg and the Ab concentration was 0.5 mg / ml. The IRF was 72+ / −2% and it was measured in Ramos cells.

[0208]Treatment of Cells

[0209]The procedure followed to treat the cells was similar to the one described in example 1. Cells were incubated during 1 hour. Control cells were prepared for each of the cell lines as described in example 1. The same amount of activity was added to the cell lines (4.6 MBq, the same activity as given in example 1). The dose to the medium of the cells was around 0.05 Gy. Every 2 to 5 days cells were split and ...

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
Timeaaaaaaaaaa
Timeaaaaaaaaaa
Currentaaaaaaaaaa
Login to View More

Abstract

The present invention relates to radioimmunoconjugates that are capable of upregulating expression of one or more antigens. The upregulated antigens can be the antigens that are targeted by the radioimmunoconjugates or different antigens expressed on the same cells. The present invention also relates to methods of treating cancer and diseases and disorders of the immune system by utilizing this enhanced expression of antigens.

Description

TECHNICAL FIELD OF THE INVENTION[0001]The present invention relates to radioimmunoconjugates that are capable of upregulating expression of one or more antigens. The upregulated antigens can be the antigens that are targeted by the radioimmunoconjugates or different antigens expressed on the same cells.BACKGROUND OF THE INVENTION[0002]The use of monoclonal antibody therapy (MAT) has been an area of great interest and strong research efforts. To be effective, MAT depends on a sufficient number of antigens per cell of which the antigens can bind to for triggering response (Sugimoto et al., 2009, Czuczman et al., 2008).[0003]The use of radioimmunotherapy (RIT) has been approved as a therapeutic option in cancer therapy (Stevens et al., 2012). Today radioimmunotherapy is mainly used in those patient experiencing relapse from chemotherapy and / or MAT (Stevens et al., 2012).[0004]It is known from the literature that high dose rate external beam irradiation can cause an increase of CD20 in ...

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): A61K51/10A61K39/395
CPCA61K51/1027A61K2039/507A61K51/1096A61K39/39558C07K16/2887C07K16/2896A61P35/00A61P35/02A61P43/00A61K2300/00A61K39/395A61K51/1093
Inventor LARSEN, ROY H.REPETTO-LLAMAZARES, ADA
Owner NORDIC NANOVECTOR
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