Soluble Universal ADCC-Enhancing Synthetic Fusion Gene and Peptide Technology and Its Use Thereof

Abstract

Novel synthetic biology-based ADCC technologies are provided that enhance or enable ADCC responses, for example, through a rationally-designed soluble universal ADCC enhancer protein (SUAEP) where a high-affinity CD3-binding domain is fused to a high-affinity Fc-binding domain. The SUAEP technology can be used to prevent or treat cancers, infectious, inflammatory or autoimmune diseases, and other diseases where elimination of diseased cells is desirable.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims priority to and the benefit of co-pending U.S. provisional patent application Serial Nos. 62 / 089,097, filed on Dec. 8, 2014, and 62 / 200,557, filed on Aug. 3, 2015, both of which are incorporated herein by reference in their entirety.TECHNICAL FIELD[0002]The invention relates to synthetic biology products and processes that can be used to enable immune effector cells, particularly, T cells, to mediate antibody-dependent cellular cytotoxicity (ADCC) as well as methods of using them in the treatment and prevention of cancer, infectious diseases, inflammatory and autoimmune diseases and other diseases.BACKGROUND OF INVENTION[0003]Mammals, especially higher vertebrates including human, have developed highly complex immune systems that use multiple mechanisms and effectors to detect, destroy, or at least contain foreign pathogens as well as diseased or stressed autologous cells. These diseased cells may have been infecte...

AI Technical Summary

Benefits of technology

The present invention introduces a novel way to enhance the body's immune response against cancer, infections, and other diseases. It involves a new type of molecule called an Adapter-like ADCC Enhancer that combines the power of T cells and antibody-based therapy. This molecule allows for the creation of high-affinity Fc receptors that can target a wide range of disease-causing antigens. This approach is much faster and more effective than traditional antigen-dependent immunotherapy, which needs to create a new antibody for each specific antigen. Overall, this invention provides a more efficient way to fight disease and improve the immune system's defense against harmful organisms and cells.

Problems solved by technology

Moreover, several clinical studies have shown that patients carrying a lower affinity variant of CD16 (F158) have worse clinical outcomes.

However, ADCC efficacy, as primarily mediated by endogenous natural killer (NK) cells, is limited in the body due to a number of physiological as well as pathological reasons as explained below (to the extent that endogenous Cytotoxic T lymphocytes participate in tumor clearance at all, their efficacy have also been found to be very limited and lacking).

First, most cells involved in ADCC such as macrophages and neutrophils do not tend to proliferate when they are activated.

NK cells also have limited proliferation potential in response to activation, and they also rapidly die off.

Therefore, natural ADCC response in the body risks being overwhelmed by disease progression (e.g., viral infection, cancer) even if the ADCC effectors recognize antibodies coating diseased cells.

Cancer cells and viruses counteract body's ADCC-based defense system by abnormally amplifying such inhibitory pathways.

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