Chimeric antigens for breaking host tolerance to foreign antigens

一种嵌合抗原、抗原的技术，应用在使用载体引入外来遗传物质、融合多肽、抗细菌药等方向，能够解决没有有效预防性或治疗性疫苗等问题

Active Publication Date: 2011-04-27
CHIMIGEN BIOMEDICAL (CHENGDU) CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

About 170 million people worldwide are chronic carriers of HCV, for which there is no effective preventive or therapeutic vaccine

Method used

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  • Chimeric antigens for breaking host tolerance to foreign antigens
  • Chimeric antigens for breaking host tolerance to foreign antigens
  • Chimeric antigens for breaking host tolerance to foreign antigens

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0149] A. Example 1: Construction of TBD expression vector

[0150] Code C H 1-Hinge-C H 2-C H The murine IgGl DNA sequence of the amino acids of the 3-region portion was produced from mRNA isolated from a hybridoma (2C12), which produced a mAb directed against the HBV surface antigen (sAg). Using Trizol Reagents (Gibco BRL cat.No.15596-026) were used to isolate total mRNA and target binding domain (TBD) was generated by reverse transcription-PCR (RT-PCR) using Superscript First-strand Synthesis (Invitrogen Cat. ; mouse immunoglobulin fragment) cDNA. The PCR primers contained a linker sequence encoding a linker peptide - SRPQGGGS- (SEQ ID NO: 1) at the 5' end, a unique Not I site at the 5' end and a unique Hint III restriction site at the 3' end. Generated cDNA contains (5'NotI)-junction sequence-C H 1 (VDKKI) (SEQ ID NO: 2).-Hinge region-C H 2-C H 3-(3'Hind III). After digestion with the corresponding enzymes, this fragment was ligated with the pFastBac HTa expressi...

Embodiment 2

[0155] B. Example 2: Construction of Chimeric Antigen Expression Vector

[0156] DNA encoding the desired viral antigen was generated from the template using the PCR method using the 5' sense and 3' antisense primers in Table 2. The resulting amplified fragments contain a unique restriction site "5' enzyme" at the 5' end and a unique restriction site "3' enzyme" at the 3' end, each of which is used for ligation.

[0157] Table 2: Construction of chimeric antigen vectors

[0158] viral antigen

sense primer

antisense primer

template

5' enzyme

3' enzyme

HBV S1 / S2

SEQ ID NO: 7

SEQ ID NO: 8

pRSET BHV S1 / S2

Bam HI

Not I

HBV S1 / S2 / S

SEQ ID NO: 9

SEQ ID NO: 10

pAlt HBV 991

Nco I

Not I

HBV core

SEQ ID NO: 11

SEQ ID NO: 12

pAlt HBV 991

Nco I

Not I

DHBV PreS / S

SEQ ID NO: 5

SEQ ID NO: 13

pFastBac Hta PreS / S

Eco RI

Not I

DHBV PreS

SEQ ID NO: 5 ...

Embodiment 3

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PUM

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Abstract

Disclosed herein are compositions and methods for eliciting immune responses against antigens. In particular, the compounds and methods elicit immune responses against foreign antigens that are otherwise recognized by the host as 'self' antigens, thus breaking host tolerance to those antigens. Presenting the host immune system with a chimeric antigen comprising an immune response domain and a target binding domain, wherein the target binding domain comprises an antibody fragment, enhances the immune response against the foreign or tolerated antigen. Antigen presenting cells take up, process, and present the chimeric antigen, eliciting both a humoral and cellular immune response against the desired antigen.

Description

[0001] related application [0002] This application claims priority to US Provisional Application No. 60 / 493,449, filed August 8, 2003, the contents of which are hereby incorporated by reference. technical field [0003] The present invention relates to methods and compositions for eliciting or enhancing an immune response (immune response) and for breaking host tolerance to foreign antigens. Background technique [0004] When a healthy host (human or animal) encounters a foreign antigen, such as a protein derived from bacteria, viruses and / or parasites, the host typically mounts an immune response. The immune response may be a humoral immune response and / or a cellular immune response. In a humoral immune response, antibodies are produced by B cells and secreted into the blood and / or lymph in response to antigenic stimulation. The antibody then neutralizes the antigen (such as a virus) by specifically binding to the surface of the antigen, labeling the antigen so that the...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12N15/62C12N15/13C12N15/36C12N15/63C12N15/10C12N15/02C12P21/02C07K16/28A61K39/29A61K47/48A61P31/12A61P31/20A61K38/095A61K39/00A61K39/385C07K14/02C07K14/18C07K16/08C07K16/46C12N5/0784
CPCA61K39/385C12N2770/24222C07K14/005A61K2039/5154C07K16/082C07K16/46A61K38/00C07K2319/73C12N2730/10122C12N5/0639C07K2319/01A61K39/00A61K2039/6056A61P31/04A61P31/12A61P31/14A61P31/18A61P31/20A61P31/22A61P33/00A61P35/00
Inventor 拉詹·乔治洛恩·蒂勒尔安托万·努杰姆王大坤马友伦
Owner CHIMIGEN BIOMEDICAL (CHENGDU) CO LTD
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