Synthetic genes that rewire natural immune pathways for anti-tumor defense

Background

Cancer is a malignant tumor resulting from the formation of abnormal cells in the body that can grow in an out-of-control fashion, eventually becoming fatal in the absence of effective, timely treatment. Interferons are a family of proteins that can naturally regulate the recognition and elimination of cancer cells by the body’s own immune cells. Studies have shown that interferons are essential in the natural immunomodulation against cancer through their effects on the expression of genes in the cancer cells which, in turn, modulate the expression of further genes in the immune cells. This process includes several specific molecular pathways that, once activated, provide potent immune response against cancer.

Recently developed cancer therapies, like T-cell based immunotherapies, aim at increasing the expression of interferons in the tumor environment to enhance anti-tumor immune response. Though proven effective through the injection of cytokines or microbial activators into the tumor, this approach has limited clinical applications due to the reliance on external sources for these factors, the possibility of missing the tumor core activation, and other possible clinical complications.

Technology Overview

To address these limitations, Dr. Kagan and his group at Boston Children’s Hospital did extensive research that revealed an innovative approach of inducing tumor immunogenicity through the activation of interferon expression by inventing novel genes that can utilize the naturally existing signaling pathways in tumors. Through the rewiring of these natural signaling pathways to induce the expression of interferons, it became possible to promote interferon-based antitumor immune response in a more specific and effective way to treat cancer. Further validation research by this group confirmed the utility of these novel genes in stimulating strong interferon response in cultured cells.

This invention is not only novel, but also a unique approach of utilizing the innate immune pathways through a genetic rewiring of these pathways. The results represent a significant advancement in the new era of precision medicine against cancer.

Applications

1. Treatment of early stages of solid cancer tumors through T-cell immunotherapy.
2. Adjuvant therapy following surgical resection of malignant tumors.
3. Treatment of advanced stages of cancer, in combination with chemotherapy and/or radiation.

Advantages

1. High specificity of innate immune system to target cancerous cells. There is a significant possibility for complete elimination (remission) following surgical resection, or in early stages of cancer.
2. High potency of immune response since it is a gene-based therapy that rewires the molecular pathways of cancer cells specifically to induce immune response.
3. Minimal side effects, due to: (a) absence of need for external cytokines and immunomodulators, and (b) reduced need for other forms of cancer therapy like radiation and chemotherapy.
4. High cost-effectiveness: unlike other cancer treatment approaches, this approach requires only the design and administration of a novel gene to reprogram novel immune response against cancer.
5. Diverse effectiveness: The ability to target different cancer types, through targeting different innate molecular pathways of cancer cell elimination.

Publications

Borden, E.C. Interferons α and β in cancer: therapeutic opportunities from new insights. Nat Rev Drug Discov 18, 219–234 (2019).