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Nanoparticle tumour vaccines

A nanoparticle, vaccine technology, applied in the field of nanoparticle-mediated delivery, which can solve the problems of discomfort and human use, high toxicity, etc.

Inactive Publication Date: 2014-07-30
MIDATECH LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Many adjuvants are considered too toxic for discomfort and human use

Method used

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  • Nanoparticle tumour vaccines
  • Nanoparticle tumour vaccines
  • Nanoparticle tumour vaccines

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0142] Example 1 - Synthesis and Characterization of Nanoparticles

[0143] The test ligands and their identification numbers are given below (molecule wt);

[0144] SIINFEKL (963) (SEQ ID NO: 87)

[0145] SIINFEKL-N-(CH 2 ) 2 -SH (1021)

[0146] FLSIINFEKL-N-(CH 2 ) 2 -SH (1280) (SEQ ID NO: 88)

[0147] FLAAYSIINFEKL-N-(CH 2 ) 2 -SH (1587) (SEQ ID NO: 89)

[0148] AAYSIINFEKL-N-(CH 2 ) 2 -SH (1325) (SEQ ID NO:90)

[0149] HS(CH 2 ) 2 -CONH-SIINFEKL (1051)

[0150] HS(CH 2 ) 2 -CONH-FLSIINFEKL (1309)

[0151] HS(CH 2 ) 2 -CONH-FLAAYSIINFEKL (1616)

[0152] HS(CH 2 ) 2 -CONH-AAYSIINFEKL (1356)

[0153] HS-(CH 2 ) 10 -(CH 2 OCH 2 ) 7 -CONH-SIINFEKL (1471)

[0154] HS-(CH 2 ) 10 -(CH 2 OCH 2 ) 7 -CONH-FLSIINFEKL (1732)

[0155] HS-(CH 2 ) 10 -(CH 2 OCH 2 ) 7 -CONH-FLAAYSIINFEKL (2034)

[0156] HS-(CH 2 ) 10 -(CH 2 OCH 2 ) 7 -CONH-AAYSIINFEKL (1774)

[0157] Test NPs were synthesized using 10 μmole of gold chloride (Aldrich484385), 30...

Embodiment 2

[0193] Example 2 - Evaluation of Presentation Assays

[0194] The T cell receptor (TCR) is on the surface of T lymphocytes and recognizes peptides in the context of the major histocompatibility complex (MHC) (1). In general, antigen-presenting cells (APCs) contain machinery to process proteins and load them onto empty MHC. While CD4+ T cells recognize MHC class II (MHC II), CD8+ T cells respond to MHC class I (MHC I). Previously, MHCII peptides were derived from endocytic components of the extracellular milieu. In contrast, MHCI is loaded with processed peptides from cellular endogenous sources (1,2).

[0195] SIINFEKL (SEQ ID NO: 87), is a peptide epitope from ovalbumin (OVA) in a protein called H-2K b are presented in the context of the murine MHCI allele (3). If OVA is expressing H-2K b SIINFEKL (SEQ ID NO: 87) is routinely presented in mouse cells. However, if OVA is provided exogenously, SIINFEKL can be presented by an alternative method called MHCI cross-presentati...

Embodiment 3

[0223] Example 3 - Nanoparticle-peptide presentation assay

[0224] The test ligands listed below were constructed and chemically attached to gold nanoparticles (GNPs) via the linkers described above.

[0225] 1. SIINFEKL (SEQ ID NO: 87)

[0226] 2. SIINFEKL-N-(CH2)2-SH

[0227] 3. FLSIINFEKL-N-(CH2)2-SH (SEQ ID NO: 88)

[0228] 4. FLAAYSIINFEKL-N-(CH2)2-SH (SEQ ID NO: 89)

[0229] 5. AAYSIINFEKL-N-(CH2)2-SH (SEQ ID NO:90)

[0230] 6. HS(CH2)2-CONH-SIINFEKL

[0231] 7. HS(CH2)2-CONH-FLSIINFEKL

[0232] 8. HS(CH2)2-CONH-FLAAYSIINFEKL

[0233] 9. HS(CH2)2-CONH-AAYSIINFEKL

[0234] 10.HS-(CH2)10-(CH2OCH2)7-CONH-SIINFEKL

[0235] 11.HS-(CH2)10-(CH2OCH2)7-CONH-FLSIINFEKL

[0236] 12.HS-(CH2)10-(CH2OCH2)7-CONH-FLAAYSIINFEKL

[0237] 13.HS-(CH2)10-(CH2OCH2)7-CONH-AAYSIINFEKL

[0238] SIINFEKL (SEQ ID NO: 87) is an epitope from ovalbumin that is presented in the context of the murine MHC I molecule H-2Kb and measured using two methods. One approach utilizes a TCR-like anti...

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Abstract

The present invention provides a vaccine for the prophylactic or therapeutic treatment of a tumour in a mammalian subject, as well as methods of using the vaccine, including in treatment of tumours and in generating a CTL response. The vaccine comprises a plurality of nanoparticles and a pharmaceutically acceptable carrier, salt or diluent. The nanoparticles comprise a core comprising a metal and / or a semiconductor atom; and a corona comprising a plurality of ligands covalently linked to the core, wherein at least a first ligand of said plurality comprises a carbohydrate moiety that iscovalently linked to the core via a first linker, and wherein at least a second ligand of said plurality comprises an epitopic peptide that is covalently linked to the core via a second linker, said second linker comprising a peptide portion and a non-peptide portion, wherein said peptide portion comprises the sequence X1X2Z1, wherein: X1 is an amino acid selected from A and G; X2 is an amino acid selected from A and G; and Z1 is an amino acid selected from Y and F, and wherein said epitopic peptide forms at least a portion of or is derived from a Tumour-Associated Antigen (TAA).

Description

field of invention [0001] The present invention relates to substances and compositions for use in peptide-based vaccine regimens, in particular nanoparticle-mediated delivery of peptides for stimulating T cell responses. Vaccine regimens are directed towards the therapeutic and prophylactic treatment of tumors such as lung cancer tumors. Background of the invention [0002] Cytotoxic T lymphocytes (CTLs) are specialized T cells that function primarily by recognizing and killing cancer or infected cells, but also by secreting proteins called cytokines that mediate a variety of effects on the immune system The soluble molecules function. Evidence suggests that immunotherapy aimed at stimulating tumor-specific CTL responses will effectively control cancer. For example, human CTLs have been shown to recognize sarcoma (Slovin, S.F. et al., J. Immunol., 137:3042-3048, (1987)), renal cell carcinoma (Schendel, D.J. et al., J. Immunol., 151: 4209-4220, (1993)), colorectal cancer (...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/48A61P35/00
CPCA61K47/6923A61K47/6929A61P35/00A61P37/04A61K39/0011A61K2039/86A61K47/50A61K9/16A61K9/141
Inventor T·雷德梅彻尔R·菲利普
Owner MIDATECH LTD
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