Biomaterials for modulating immune responses

A technology of immune cells and compositions, applied in vaccines, drug combinations, drug delivery, etc., can solve the problems of scarce dendritic cells and slow research

Pending Publication Date: 2019-11-05
PRESIDENT & FELLOWS OF HARVARD COLLEGE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Research focused on using dendritic cells for therapeutic benefit has been slow because dendritic cells are rare and difficult to isolate

Method used

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  • Biomaterials for modulating immune responses
  • Biomaterials for modulating immune responses
  • Biomaterials for modulating immune responses

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0624] Example 1: Mesoporous silica (MPS) vaccine for enhancing anti-tumor immunity

[0625]Biomaterials have shown great potential to synergistically integrate with existing cancer vaccine strategies and enhance their effectiveness. We have recently developed injectable biomaterial vaccines through the spontaneous assembly of mesoporous silica (MPS) microparticles into 3D scaffolds in vivo. When formulated with GM-CSF and CpG, MPS vaccines modulate host dendritic cell (DC) activation and trafficking. Here we demonstrate that a single injection of MPS vaccine induces persistent germinal center activity over 30 days, for example in draining lymph nodes. Thus, when immunized with a small linear Her2 / neu peptide within the binding domain of trastuzumab, the MPS vaccine elicited more than 2 orders of magnitude higher IgG1 and IgG2a antibody titers than the bolus vaccine, and the antibodies were Native Her2 is structurally shown to be responsive to breast cancer cells. To furt...

Embodiment 2

[0626] Example 2: D,L-lactide and glycolide (PLG) scaffolds comprising PEI

[0627] Coating of PLG scaffolds with polyethyleneimine (PEI) enhanced dendritic cell (DC) activation. Application of PEI to the PLG system prior to antigen adsorption enhanced antitumor responses in cancer vaccine models.

[0628] Compared with the control, the scaffold loaded with PEI promoted TLR5 activity to increase 3-4 times in vitro ( Figure 19A ). Furthermore, murine DCs seeded on PEI-PLG scaffolds produced more than 3-fold more IL-12 and approximately 30-fold more IFN-α than cells seeded on scaffolds without PEI ( Figure 19B ). These results suggest that PEI-modified PLG can locally activate DCs and other antigen-presenting cells, APCs, possibly through the TLR5 pathway.

[0629] Antigens from B16-F10 melanoma tumor lysates were adsorbed onto the PEI-PLG system to generate cancer vaccines. Implantation of PEI-antigen-coated vaccines into mice induced local production of in situ immuno...

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Abstract

The provided herein are methods and compositions for eliciting an immune response to an antigen, such as cancer and microbial antigens.

Description

[0001] related application [0002] This application requires U.S. Provisional Application No. 62 / 473,699 filed March 20, 2017, U.S. Provisional Application No. 62 / 460,652 filed February 17, 2017, and August 2, 2016 under 35 U.S.C. § 119(e) Priority benefit of U.S. Provisional Patent Application No. 62 / 370,211 filed on , each of which is incorporated herein by reference in its entirety. [0003] governmental support [0004] This invention was made with Government support under Grant No. R01EB015498 awarded by the National Institutes of Health. The government owns certain rights in inventions. [0005] Reference Sequence Listing [0006] The content of the text file named "29297-132001WO_SEQUENCE_LISTING_ST25.txt" created on August 2, 2017 is 292 kilobytes, filed as part of this application, and incorporated herein by reference in its entirety. Background technique [0007] Dendritic cells (DCs) collect and process antigens for presentation to T cells. DCs are the mo...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/39A61K9/16A61K39/00
CPCA61K39/39A61K9/0019A61K9/5031A61K2039/5154A61K2039/545A61K2039/55522A61K2039/55555A61K2039/55561A61K2039/572A61K2039/6056A61P35/00A61K39/00119A61K2039/876A61K39/001106A61K39/0011A61K39/385A61K2039/6093A61K2039/57A61K9/16A61K2039/812A61K47/02A61K47/34A61K2039/54
Inventor D·J·穆尼李玮薇O·A-R·阿里石庭宇
Owner PRESIDENT & FELLOWS OF HARVARD COLLEGE
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