Methods of immune modulation against foreign and/or auto antigens

An antigen and immune checkpoint technology, applied in the field of immune regulation against foreign antigens and/or self-antigens, can solve the problems of lack of tumor antigen-reactive clones, low response rate, etc.

Pending Publication Date: 2019-11-29
唐泽群
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the exact mechanism leading to the low response rate is unknown, one potential mechanism may be the absence of tumor antigen-reactive clones in the patient's T cell repertoire prior to immune checkpoint inhibitor therapy

Method used

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  • Methods of immune modulation against foreign and/or auto antigens
  • Methods of immune modulation against foreign and/or auto antigens
  • Methods of immune modulation against foreign and/or auto antigens

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0235] Utilize one or more guide RNAs targeting human PDL1, CRISPR-Cas9 protein, and antigenic protein β-amyloid protein with the sequences in Table 2 below to design and construct plasmids:

[0236] Table 2.

[0237]

[0238]

[0239] The CRISPR-Cas9 protein is expressed under the control of the CMV promoter, the guide RNA is expressed by the T7 promoter, and the β-amyloid protein is expressed under the control of the hEFla promoter, such as figure 1 drawn in. although figure 1 Single plasmid constructs are shown, but expression of these elements in multiple DNA plasmids is also within the scope of the invention. The plasmid is delivered to a patient suffering from, for example, Alzheimer's disease. Current vectors can be chemically synthesized based on publicly available sequence information.

Embodiment 2

[0241] Single plasmids were constructed as described in Example 1 above using guide RNA targeting PDL1 and / or CTLA4 (Table 1 above), CRISPR-Cas9 protein, and Her2 / Neu. figure 2 Depicted is a single plasmid in which the CRISPR-Cas9 protein is expressed from the CMV promoter, the guide RNA is expressed from the T7 promoter, and Her2 / Neu is expressed from the h-EFla promoter. Such compositions can be used to treat diseases such as, but not limited to, breast cancer or other Her2 / Neu expressing cancers.

Embodiment 3

[0243] Single plasmids were constructed as described in Example 1 above using guide RNA targeting PDL1 and / or CTLA4 (Table 1 above), CRISPR-Cas9 protein, and Her2 / Neu. figure 2 Depicted is a single plasmid in which the CRISPR-Cas9 protein is expressed from the CMV promoter, the PDL1 guide RNA is expressed from the T7 promoter, the CTLA4 gRNA is expressed under the control of the promoter, and Her2 / Neu is expressed from the h-EFla promoter.

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Abstract

The present invention is directed to compositions and methods of treating proliferative disorders, such as cancer, using a composition comprising an immune checkpoint antagonist and an antigen. It hasbeen found that the composition elicits an immune response allowing an otherwise suppressed immune system to activate in order for T cells to attack cancer cells. Compositions may be presented in a vector comprising nucleic acids encoding the antagonist and antigen, and may include gene editing systems, such as CRISPR-Cas9 system.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of priority to US Application Serial No. 62 / 451,759, filed January 29, 2017, under 35 U.S.C. 35 USC § 119(e). The disclosure content of this priority application is considered part of the disclosure content of the present application and is incorporated by reference into the disclosure content of the present application. technical field [0003] The present invention relates to enhancing the immune response to foreign or self-antigens and can be used to increase the efficacy of therapeutic and / or prophylactic vaccines for a variety of diseases including cancer, infectious diseases, neurodegenerative diseases, Autoimmune disease, transplant rejection, and animal autoimmune disease model generation. Specifically, this paper describes the development of novel tumor vaccine platforms that combine antigen expression with modulation of immune checkpoint-associated proteins within antigen-pr...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/39C07K16/28C07K14/705C07K16/30A61P37/04
CPCA61K39/39A61P37/04A61K39/00A61K39/0007A61K2039/505A61K2039/53A61K39/001106A61P35/00A61K39/0011A61K39/001162A61K2039/5154A61K2039/5156A61K2300/00A61K39/0008A61K39/08A61K39/104
Inventor 唐泽群
Owner 唐泽群
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