Programmed Self-assembly of a Peptide-MHC Dynamic Anchor for Antigen-specific Immune Modulation

Unmet Need: Use of T-cells in the eradication of diseases has been limited by the inability to produce or enhance activation of desired T-cell populations to an antigen of interest, ultimately leading to disease progression.

Technical Details: Johns Hopkins researchers have developed novel fusion constructs that produce and/or enhance T-cell activation to an antigen of interest, useful to generate targeted T-cell activation against lasting diseases including infections and cancer. An antigen portion specific to the disease target of interest is fused to a soluble Major Histocompatibility Complex (MHC) molecule, followed by a dynamic anchor molecule that targets the product to T-cells of interest. As shown in mice, the compound utilizes the dynamic anchor to firmly stabilize interactions at the T-cell receptor – pMHC interface and senses the microenvironment in order to self-assemble and amplify activation of T-cells by cross-linking T-cell receptors. The product is extremely versatile in that any antigen of interested can be utilized and both T-cell subsets (CD4+ T-cells or CD8+ T-cells) can be activated for productive immune responses. Production occurs using recombinant DNA technology and established isolation methods so that each component can be efficiently customized and purified for a variety of pathogen or cancer targets.

Value Proposition:

• T-cell activating product can be broadly applied in therapeutic contexts for infections and cancer
• Utilizes well-established recombinant protein production and isolation methods that result in highly versatile pharmaceutical products
• Useful in combination with existing anti-pathogen and anti-cancer treatment strategies to improve disease outcomes

Looking for Partners to: Develop & commercialize the technology as an agent to enhance antigen-specific T-cell responses against a broad range of diseases including infections and cancer in order to improve disease outcomes. 

Stage of Development: Pre-Clinical

Data Availability: Animal data

Inventors: T.C. Wu, Chih-Ping Mao, Chien-Fu Hung

Patent Status: Pending: 15/555,613

Publication: Mao CP, Peng S, Yang A, He L, Tsai YC, Hung CF, Wu TC. (2018) Programmed self-assembly of peptide-major histocompatibility complex for antigen-specific immune modulation. PNAS 115(17): E4032-E4040.

 

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