Eureka AIR delivers breakthrough ideas for toughest innovation challenges, trusted by R&D personnel around the world.

Modulated Immunodominance Therapy

a technology of immunodominance and immunomodulation, applied in the field of cancer, chronic infections, autoimmune diseases, transplantation, etc., can solve the problems of unfavorable primary immunosuppressive environment and inability to create a profile of immune response on a routine clinical basis, so as to alter the immunodominance hierarchy of patients and alter the immunodominance hierarchy

Inactive Publication Date: 2014-04-10
GENEIUS BIOTECH
View PDF0 Cites 5 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

This patent describes a way to change the way the immune system responds to disease. It involves identifying specific parts of the disease and training the immune system to recognize them. This can be done before or after a person is exposed to the disease. This invention could have a significant therapeutic benefit for cancer, chronic infections, autoimmunity, and transplantation. It works by rebalancing the immune response to the disease.

Problems solved by technology

However, creating a profile of the immune response has not been done on a routine clinical basis.
It is also well known that tumors and infectious agents create an immunosuppressive environment which is not optimal for a strong primary immune response.

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
  • Modulated Immunodominance Therapy
  • Modulated Immunodominance Therapy
  • Modulated Immunodominance Therapy

Examples

Experimental program
Comparison scheme
Effect test

example 1

1. Example 1

EBV Latent Infection, Lymphomas and Nasopharyngial Carcinoma

[0161]90% of the world's population has been exposed to EBV (the causative virus in mononucleosis) as measured by antibodies in the blood. EBV becomes latent in B cells and shuts off the majority of its proteins but express very low levels of latent antigens LMP1, LMP2 and sometimes EBNA-1. These proteins are weakly immunogenic but are required to maintain the virus even in its latent state. Because they derive predominantly from B cells, 40% of lymphomas test positive for EBV latent antigens. Thus, these antigens can serve as targets for the generation of CTL responses in adoptive cell therapy. In addition, Nasopharyngial carcinoma also expresses EBV latent antigens as do other tumors (e.g. −10% of gastric cancer). While CTL's have been used to treat EBV lymphomas, the current production methods are time consuming (3-6 months) and cumbersome using B cells transformed with EBV as repeat stimulation. Further, CTL...

experiment 1

a. Experiment 1

The Relative Frequency of T Cells Responding to Subdominant Epitopes is Enhanced when Dendritic Cells or Activated Macrophages are Used as Antigen Presenting Cells Instead of LCL

[0166]T cell lines were prepared from 10 patients using 3 different antigen presenting cells as stimulators: EBV transformed lymphoblastoid cell lines (LCL) presentation and expansion; Dendritic cell (DC) presentation with cytokine expansion; IFNγ Macrophage (MAC) presentation with cytokine expansion. Each of the 3 were stimulated during antigen presentation with a mixture of 3 plasmids expressing subdominant epitopes of EBNA-1 (EBNA-1 with deletion of aa 90 to 325), LMP1 (LMP1 with deletion of aa 1-43 and aa 260-315) and LMP2 (LMP2A in 2 plasmids one expressing aa 1-399 and the second plasmid expressing aa 400-497). The T cell lines so generated using the protocol of the invention were then studied in 51Cr release assay.

[0167]FIGS. 1A and 1B: 51Cr release at two different effector:target (E / T...

example 2

b. Example 2

[0191]In the following experiments, T cells were grown in the same way as outlined in Example 1 above, with different variations designed to enhance antigen processing to favor T cells reactive with the production of subdominant epitopes.

[0192]FIG. 7: (51Cr release) Cr release at 20:1 effector:target (E / T) ratios (CTL Lines: HLA matched fibroblasts) HLA matched fibroblasts pre-pulsed with peptides representing Dominant antigen (EBNA-3A), Subdominant antigen (LMP2) and specific HLA A2 restricted subdominant epitopes from LMP2 with CTLs made from the same patient using two different methods: one with 100 nM to 300 nM bortezomib added during antigen presentation, one without.

[0193]Conclusion: Addition of the Proteosome antagonist bortezomib during CTL antigen presentation modifies antigen processing to generate CTL's to a broader number of subdominant epitopes with a modest decrease in the response to dominant epitopes

[0194]FIG. 8: (51Cr release) Cr release at 20:1 effector...

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
Responsivityaaaaaaaaaa
Immunogenicityaaaaaaaaaa
Login to View More

Abstract

The invention involves generating a T cell response to subdominant antigens and using the cells to therapeutically change the cellular homeostasis and nature of the immune response. In a preferred embodiment, the cells are generated outside of the patient avoiding the influence of the patient's immunologic milieu. By stimulating and growing the T cells from a patient in a tissue culture to one or more subdominant antigens and the transplanting them into the patient, if enough cells are expanded and transplanted, the transplanted cells overwhelm the endogenous dominant T cells in the response to either break or induce immune tolerance or otherwise modify the immune response to the cells or organism expressing that antigen. When the memory cells are established they are then reflective of this new immunodominance hierarchy so that the desired therapeutic effect is long lasting. In effect, the transplantation exogenously generated T cells reactive to the subdominant antigens is recapitulating priming and rebalancing the patient's immune response to target previously subdominant antigens in the cells or organism to produce a therapeutic benefit.

Description

RELATED APPLICATIONS[0001]This application is a national stage application, filed under 35 U.S.C. §371, of International Application No. PCT / US2012 / 039605, filed on May 25, 2012, which is related to provisional application U.S. Ser. No. 61 / 490,505, filed on May 26, 2011, the contents of which are hereby incorporated by reference in its entirety.BACKGROUND OF THE INVENTION[0002]The present invention relates to a novel therapeutic for cancer, chronic infections, autoimmune diseases, and transplantation based upon the modification of the immunodominance hierarch by therapeutic manipulation of cellular homeostasis.[0003]The clinical management of cancer is specific for each site of origin and, for the most part, depends upon stage of the disease (i.e., how far the tumor has invaded locally or spread to other organs by metastasis). Surgery and / or localized radiotherapy are generally the treatment of choice for the primary tumor with chemotherapy, monoclonal antibody or cytokine therapy o...

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): A61K35/14A61K39/00
CPCA61K35/17A61K39/292C12N2730/10134A61K39/12A61P29/00A61P35/00A61P37/00A61P37/02A61P37/06C12N5/0636A61K39/4611C12N2502/1157C12N2502/1121C12N2501/2302C12N2501/2307A61K39/464838C12N2710/16011C12N2501/999A61K2239/53A61K2239/31A61K39/46433A61K2239/48A61K39/4621A61K39/464486A61K2239/38A61K39/4622A61K39/464484A61K39/464488A61K39/464491A61K39/4615C12N5/06C12N5/0617A61K39/245A61K39/29A61P31/00A61K2239/46A61K2039/55566A61K39/0008A61K2039/5158A61K2039/53A61K39/0011A61K2039/585C12N2710/16034C12N2730/10171C12N7/00C12N2710/16234A61K9/0019C12N2501/2304C12N2501/2306C12N2501/2312C12N2501/2315C12N2501/2321A61K9/0021A61K2035/124
Inventor SLANETZ, ALFRED E.
Owner GENEIUS BIOTECH
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
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