Related Experiment Video
Updated: Mar 13, 2026
08:36
In Vitro Assay to Study Tumor-macrophage Interaction
Published on: August 1, 2019
8.1K
Genetically Engineered Macrophages: A Potential Platform for Cancer Immunotherapy
Kara W Moyes1, Nicole A P Lieberman1, Shannon A Kreuser1
11 Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute , Seattle, Washington.
Human Gene Therapy
|October 21, 2016
Summary
Genetically engineered macrophages (GEMs) can overcome the glioblastoma tumor microenvironment, enhancing immune responses. This novel platform shows potential for treating glioblastoma and other challenging tumors.
Area of Science:
- Immunotherapy
- Oncology
- Cellular Engineering
Background:
- Immunotherapy has shown success in hematologic malignancies but not glioblastoma (GBM).
- The GBM tumor microenvironment suppresses immune responses, hindering treatment efficacy.
- A novel macrophage-based platform is proposed to overcome these challenges.
Purpose of the Study:
- To develop and validate a genetically engineered macrophage (GEM) platform for glioblastoma immunotherapy.
- To assess the stability and safety of GEMs in vitro and in vivo.
- To demonstrate the versatility of GEMs in modulating the tumor microenvironment and immune responses.
Main Methods:
- Utilized a lentiviral expression system to generate transduced monocytes and macrophages.
- Validated transgene expression stability in vitro and in a mouse xenograft model of GBM.
- Engineered GEMs to secrete immune-modulating proteins (e.g., soluble TGF-β receptor II, IL-21) and utilized CRISPR to knock out immunosuppressive genes (e.g., IL-10, PD-L1).
Main Results:
- Transgene expression in GEMs was stable for weeks to months.
- GEMs did not cause morbidity or accelerate tumor growth in animal models.
- GEMs demonstrated the ability to reduce immune suppression and promote immune cell activation.
- CRISPR-mediated gene knockout in GEMs showed potential to enhance cytotoxic cell function.
Conclusions:
- Genetically engineered macrophages (GEMs) represent a promising cell-based platform for transforming the tumor microenvironment.
- GEMs can enhance innate and adaptive antitumor immunity, offering a potential therapeutic strategy for glioblastoma.
- The GEM platform's versatility suggests broad applicability to other tumors with immunosuppressive microenvironments.
Related Concept Videos
01:27Tumor Immunotherapy
2.1K
Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
2.1K
02:43Mouse Models of Cancer Study
6.7K
Mice have long served as models for studying human biology and pathology because of their phylogenetic and physiological similarity with humans. They are also easy to maintain and breed in the laboratory, and hence, many inbred strains are now available for research. Studies on mice have contributed immeasurably to our understanding of cancer biology.
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...
6.7K