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Combination immunomodulation and uses thereof

A composition and a technology of combining fragments, applied in the field of combined immune regulation and its use, can solve the problems of insufficient immune response and the like

Pending Publication Date: 2022-04-29
OHIO STATE INNOVATION FOUND
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

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Method used

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  • Combination immunomodulation and uses thereof
  • Combination immunomodulation and uses thereof
  • Combination immunomodulation and uses thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0152] Example 1. Nanoparticle (NP)-OX40 mRNA induces increased expression levels of OX40

[0153] Characterization of OX40 expression in EG.7-OVA cells. Nanoparticle (NP)-OX40 mRNA induced much higher OX40 expression compared to the control group ( figure 1 ). 5'UTR and 3'UTR modifications are broadly applicable to mRNAs encoding cytokines and immune checkpoint regulators (such as ICOS, 4-1BB, GITR, CD40, etc.). Nanoparticles were formulated with lipids, DOPE, cholesterol, DMG-PEG, and mRNA (see Li, B et al., An Orthogonal array optimization of lipid-like nanoparticles for mRNA delivery in vivo. Nano Lett. 2015, 15, 8099-8107 ).

Embodiment 2

[0154] Example 2. Combination therapy of NP / OX40 mRNA + anti-OX40 antibody improves tumor therapy in a B16 melanoma tumor model.

[0155] A mouse tumor model of B16 melanoma was established (Triplett, TA et al., Reversal of IDO-mediated cancer immunopression by systemic kynurenine depletion with treatment enzyme, Nat Biotechnol. 2018 Sep;36(8):758-764). Mice were treated with PBS, NP+anti-OX40 antibody (InVivoPlus anti-mouse OX40 (clone OX-86) (company: BioXcell, catalog: BP0031)) or NP / OX40 mRNA+anti-OX40 antibody. In this mouse tumor model, the combination of these mRNAs and their associated antibodies significantly improved tumor therapy ( Figure 2A ) and prolonged overall survival ( Figure 2B ).

Embodiment 3

[0156] Example 3. Combination therapy of NP / OX40 mRNA + anti-OX40 antibody improves tumor therapy in CT26 tumor model.

[0157] A CT26 mouse tumor model was established (Malvicini, M et al., Tumor Microenvironment Remodeling by 4-Methylumbelliferone Boosts the Antitumor Effect of Combined Immunotherapy in Murine Colorectal Carcinoma, Molecular Therapy. Vol. 23 No. 9, 1444-1455, September 2015). Mice were treated with PBS, nanoparticles (NP)+anti-OX40 antibody, nanoparticles (NP) / OX40 mRNA+anti-OX40 antibody, and nanoparticles (NP) / OX40 mRNA+anti-OX40 antibody together. Nanoparticles (NP) / OX40 mRNA+anti-OX40 antibody (injection interval: 6 hours); and nanoparticles (NP) / OX40 mRNA+anti-OX40 antibody together (injection interval: 0 hours). The OX40 antibody used was InVivoPlus anti-mouse OX40 (clone OX-86) (company: BioXcell, catalog: BP0031)). The combination of these mRNAs and their associated antibodies significantly prolonged overall survival and improved tumor therapy in th...

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Abstract

The present disclosure relates to compositions and methods for modulating the immune system and for treating cancer and other immune disorders.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of U.S. Provisional Application No. 62 / 823,184, filed March 25, 2019, which is expressly incorporated herein by reference. [0003] Statement Regarding Federally Sponsored Research [0004] This invention was made with government support under Grant No. R35GM119679 awarded by the National Institutes of Health. The government has certain rights in this invention. technical field [0005] The present disclosure relates to compositions and methods for modulating the immune system and for treating cancer and other immune disorders. Background technique [0006] Immunotherapy has become a revolutionary strategy for treating a variety of diseases, including various types of cancer. As key immunomodulatory molecules and immune signals are identified and formulated as therapeutics, well-known cancer models can be used to test the clinical effectiveness of such therapeutics. Immunotherapy...

Claims

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Application Information

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IPC IPC(8): A61K39/395A61K48/00A61K47/68A61P35/00A61P35/04B82Y5/00C07K16/28
CPCA61K48/0033A61K48/005A61K47/6891B82Y5/00A61K39/3955C07K16/2878A61K2300/00A61P35/00A61K9/127A61K31/7115
Inventor 董一洲李文清张诚翔
Owner OHIO STATE INNOVATION FOUND