Invented by Ross Kedl, Phillip J. Sanchez, Catherine Haluszczak, University of Colorado

the immune response. Introduction The field of immunotherapy has revolutionized cancer treatment by harnessing the power of the immune system to target and eliminate cancer cells. One promising approach in this field is the combination of CD40-agonist antibodies with type 1-interferon (IFN) to enhance the immune response against cancer. This article explores the market potential for CD40-agonist antibody/Type 1-IFN synergistic combination, conjugates, and their use as therapeutics to enhance the immune response. Understanding CD40 and Type 1-IFN CD40 is a cell surface receptor found on various immune cells, including dendritic cells, B cells, and macrophages. Activation of CD40 triggers a cascade of immune responses, including the release of pro-inflammatory cytokines, activation of antigen-presenting cells, and stimulation of T-cell responses. CD40-agonist antibodies mimic the natural ligand of CD40, leading to enhanced immune activation. Type 1-IFNs, including IFN-alpha and IFN-beta, are a group of cytokines that play a crucial role in regulating the immune response. They have been used for decades in the treatment of various diseases, including viral infections and certain cancers. Type 1-IFNs stimulate the immune system by enhancing antigen presentation, promoting T-cell activation, and inducing the production of other immune-stimulating molecules. Synergistic Combination and Conjugates Recent research has shown that combining CD40-agonist antibodies with Type 1-IFNs can have a synergistic effect on the immune response. The combination enhances the activation of dendritic cells, leading to increased antigen presentation and T-cell activation. This synergistic effect has been observed in preclinical studies and is now being evaluated in clinical trials. To further enhance the efficacy and stability of the CD40-agonist antibody/Type 1-IFN combination, researchers have developed conjugates. Conjugates are molecules that combine the CD40-agonist antibody and Type 1-IFN into a single entity. These conjugates improve the pharmacokinetics and biodistribution of the therapeutic agents, leading to enhanced immune activation and tumor targeting. Market Potential and Therapeutic Applications The market potential for CD40-agonist antibody/Type 1-IFN synergistic combination, conjugates, and their use as therapeutics is significant. The global cancer immunotherapy market is projected to reach $126.9 billion by 2026, with a compound annual growth rate of 14.5%. The demand for innovative and effective immunotherapies is driving the growth of this market. The CD40-agonist antibody/Type 1-IFN combination offers several advantages over existing immunotherapies. It has the potential to enhance the immune response against a wide range of cancers, including solid tumors. Additionally, the synergistic effect of the combination allows for lower doses of each agent, reducing the risk of side effects and improving patient tolerance. Furthermore, the development of conjugates improves the stability and bioavailability of the therapeutic agents, making them more suitable for clinical use. Conjugates also enable targeted delivery of the CD40-agonist antibody and Type 1-IFN to the tumor microenvironment, increasing their efficacy and reducing off-target effects. Conclusion The market for CD40-agonist antibody/Type 1-IFN synergistic combination, conjugates, and their use as therapeutics to enhance the immune response is poised for significant growth. The combination offers a promising approach to improve the efficacy of cancer immunotherapy and has the potential to revolutionize cancer treatment. As research progresses and clinical trials yield positive results, the demand for these innovative therapeutics is expected to increase, driving market growth and benefiting patients worldwide.

The University of Colorado invention works as follows

A synergistic adhuvant” is provided, comprising synergistically-effective amounts of at lease one type 1 interferon, and at least a CD40 agonist. These moieties can be present in the same composition or separately. These fusion proteins and DNA conjucates also contain the type 1 interferon/CD40 antagonist/antigen combination. These compositions, proteins and DNA conjugates can be used as adjuvants to treat chronic diseases like HIV infection or enhance the efficacy (therapeutic and prophylactic) of vaccines.

Background for Cd40-agonist antibody/type 1-interferon synergistic combination, conjugates and use thereof as therapeutic to enhance cell immunity

Applications” of the invention

Inventors’ Rationale

Materials and methods used in some of the following examples.

EXAMPLE 1

CD8+T Cell Expansion After Combined TLR/CD40 Antigen Immunization Demonstrates Varying Dependence on IFN?

EXAMPLE 2

CD8+T Cell Expansion following Combined TLR/CD40 antagonist Immunization is Recovered In CD4-Depleted IFNS” “R KO hosts

EXAMPLE 3

Role and CD8+ Response of TNF Ligands in IFN?” ?R KOs

EXAMPLE 4

Materials & Methods

EXAMPLE 5

Immune cell response Following recombinant IFN” +/? Anti-CD40 in Mice

Materials & Methods

EXAMPLE 6

Combined Administration of Type 1 Interferon Antibody and CD40 Antibody Induce CD70+ expression on DCs.

EXAMPLE 7

Combined Administration of Increasing Amounts of Alpha IFN with and without CD40 Agonistic antibody

EXAMPLE 8

Percentage Antigen Specific T cells in Mice Immunized With Decreasing Doses Of IFN Alpha And CD40 Agonist Or Anti-CD70

EXAMPLE 9

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