Bacteria-Based Backpacks to Enhance Adoptive Macrophage Transfer against Solid Tumors

Area of Science:

• Immunology
• Oncology
• Biotechnology

Background:

• Adoptive cell therapy shows promise for cancer treatment but faces challenges with solid tumors.
• Adoptively transferred macrophages often shift from antitumor to protumor phenotypes in the immunosuppressive tumor microenvironment, limiting efficacy.
• Solid tumors create an immunosuppressive environment that hinders effective cancer immunotherapy.

Purpose of the Study:

• To develop a novel strategy to enhance the efficacy of adoptive macrophage therapy against solid tumors.
• To leverage bacterial immunogenicity for sustained macrophage activation and control of cellular phenotypes in vivo.
• To investigate the potential of bacteria-as-backpacks approach for cancer immunotherapy.

Main Methods:

• Engineered macrophages by attaching bacteria (Mø@bac) using adhesive nanocoatings.
• Evaluated the ability of Mø@bac to provide durable stimulation and control macrophage phenotypes in vivo.
• Assessed the repolarization of endogenous tumor-associated macrophages and the resulting immune response in a murine 4T1 cancer model.

Main Results:

• Mø@bac demonstrated sustainable control of macrophage cellular phenotypes in vivo.
• The Mø@bac strategy successfully repolarized endogenous tumor-associated macrophages, enhancing the immune response.
• Significant reduction in tumor progression was observed in the murine 4T1 cancer model with Mø@bac treatment, showing no adverse side effects.

Conclusions:

• Attaching bacteria to macrophages (Mø@bac) offers a viable strategy for durable macrophage stimulation and improved cancer therapy.
• The bacteria-as-backpacks approach represents a novel method to overcome the limitations of adoptive cell therapy in solid tumors.
• This innovative cell therapy modality holds potential for developing more effective cancer treatments by modulating the tumor microenvironment.