SUMMARY:
UCLA researchers in the Department of Bioengineering have developed a small and biodegradable implant that when placed adjacent to solid tumors, enhances immune response to cancer cells.
BACKGROUND:
The body’s immune system uses proteins called antibodies to train the immune response to foreign pathogens. This mechanism can combat cancerous cells in the body, but newly discovered pathways of immune evasion by cancerous cells limits the ability of the body to eliminate them. Recent efforts in therapeutics to combat immune cell evasion have focused on: flagging cancer cells to the immune system by surface marker binding and releasing the natural checkpoints of immune cell activation for increased immune response. While these treatments have shown initially promising results in patients, there is a growing cohort of patients that have cancers that develop immunity to treatments. These immunomodulating drugs have also shown serious side effects: severe inflammation and susceptibility to infection. While the precise mechanism for the development of these side effects is currently unknown, a growing body of evidence suggests that the systemic immunoregulation of these initially effective cancer therapies could be the root cause. Due to this growing body of evidence, 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 small and biodegradable implant that when placed adjacent to solid tumors, enhances immune response to cancer cells. The biodegradable implant is functionalized with a collection of nanoparticles with cytokine containing cargo. Recent literature has shown that the presence of regulatory T-cells (Tregs), are likely to interfere with the anti-tumor T-cell response; the use of cytokines can suppress Treg function. Once implanted, the matrix of nanoparticles slowly releases its cytokine payload over the course of 5 days. This sufficient time frame allows greater T-cell activity at the site of the solid tumor. Researchers also found that the implanted matrix is degraded by the body within 15 days, ridding of the need for surgical extraction at the end of the therapeutic intervention. This technology presents a first in line method to combat common side effects from systemic immunomodulation for cancer therapy while preserving enhanced immune response to cancer cells.
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 cytokine release to local tumor
DEVELOPMENT-TO-DATE:
The treatment has been tested in vivo and shown efficacy for solid tumor reduction.
PCT PUBLICATION: WO2021055658 IMPLANIMPLANTABLE SCAFFOLDS AND USES THEREOF FOR IMMUNOTHERAPY OTHER USES
RELATED PAPERS (from the inventors only):
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. 10.1002/adma.201703178
KEYWORDS: 3D Scaffold, Cytokine, Local Release, T-Cell Activity, Solid Tumor, Immunotherapy, Treg