UCLA researchers in the Department of Bioengineering have developed a treatment to introduce local immunomodulation factors, that overcome the side effects associated with systemic cancer immunology treatments.
BACKGROUND:
When the body’s immune system encounters foreign pathogens, proteins called antibodies are produced to fight infection. Through the course of a day, the immune system is exposed to billions of germs, and the immune system can educate itself to harmful pathogens. Recent research has even shown that the immune system can target cancerous cells, attacking them through two main pathways: flagging of cancer cells to the immune system by surface marker binding and releasing the natural checkpoints of immune cell activation for increased immune response. Though the past decade of research in cancer immunology have discovered important mechanisms for continued bodily response to tumor cells, the use of a systemic immunomodulator has shown significant side effects. Current immunomodulators on the market can cause: severe inflammation, provocation of autoimmunity, and susceptibility to infection. There is a growing interest for the development of local introduction of factors for the decreased incidences of systemic immunomodulation, but currently there are no advances.
INNOVATION:
UCLA researchers in the Department of Bioengineering have developed a treatment to introduce local immunomodulation factors, that overcome the side effects associated with systemic cancer immunology treatments. The researchers developed artificial “cells” that produce proteins required for the biosynthesis of signaling factors known as cytokines. This artificial biosynthetic process displays several features not obtainable by conventional biological systems: tunable initiation to eliminate systemic toxicity of basal/continuous expression, controlled release to locally focus the site of cytokine activity and targeting to attach the “cells” to T-cells. The researchers implemented this treatment in a mouse model to tune T-cell fate and promote clearance of cancer. Maximal biosynthesis of cytokines was observed after 60 minutes, and showed T-cell activation, proliferation, and killing enhancement of cancerous cells. These results show the potential of the treatment as a new therapeutic approach to cancer immunotherapy without systemic side effects observed with current strategies.
POTENTIAL APPLICATIONS:
• The mitigation of systemic effects associated with current cancer immunology treatments
• Localized immunomodulation for cancer therapy
• Enhanced immunotherapy for solid tumors
ADVANTAGES:
• On demand production and release of therapeutic proteins at the site of immunological action
• Ability to synthesize specific factors in situ while also controlling timing and spatial delivery not currently achievable in biological systems
• Tunable initiation to eliminate systemic toxicity of basal/continuous expression
• Controlled release to locally focus the site of cytokine activity
• Ability to target artificial “cells” to T-cells for increased activation and killing
DEVELOPMENT-TO-DATE:
The treatment was first tested in a co-culture of T-cells and melanoma cells, that was monitored by flow cytometry to understand increased T-cell killing potential. Initial promising results were followed up in vivo and confirmed to hold therapeutic promise in solid tumors.
RELATED PAPERS:
Majedi FS, Hasani‐Sadrabadi MM, Kidani Y, Thauland TJ, Moshaverinia A, Butte MJ, Bensinger SJ, Bouchard LS. Cytokine Secreting Microparticles Engineer the Fate and the Effector Functions of T‐Cells. Advanced Materials. 2018 Jan 8.