Polymer Backpack-Loaded Tissue Infiltrating Monocytes for Treating Cancer

Area of Science:

• Immunotherapy
• Cancer Biology
• Biomaterials Engineering

Background:

• Solid tumors present challenges for adoptive cell therapies due to poor infiltration and immunosuppressive microenvironments.
• Myeloid cells, abundant in tumors like triple-negative breast cancer, are promising therapeutic targets but exhibit plasticity.
• Antigen-independent strategies are needed to overcome tumor heterogeneity and non-response.

Purpose of the Study:

• To develop a novel therapeutic strategy leveraging monocyte trafficking for solid tumor treatment.
• To control monocyte differentiation within the tumor microenvironment using engineered biomaterials.
• To investigate the potential of OPTIMs in reducing tumor burden and improving survival.

Main Methods:

• Adoptive transfer of monocytes engineered with surface-adherent "backpacks" containing interferon gamma (IFNγ).
• Development of Ornate Polymer backpacks on Tissue Infiltrating Monocytes (OPTIMs) to induce pro-inflammatory macrophage phenotypes.
• Treatment of 4T1 tumor-bearing mice with OPTIMs and subsequent analysis of tumor burden, survival, and tumor microenvironment.

Main Results:

• OPTIMs treatment significantly reduced tumor burden in the 4T1 mouse model.
• Therapy with OPTIMs led to a significant increase in animal survival.
• Immune and cytokine profiling demonstrated that OPTIMs remodeled the tumor microenvironment towards a pro-inflammatory state.

Conclusions:

• OPTIMs represent a promising antigen-independent approach for treating solid tumors.
• Engineering myeloid cell plasticity via biomaterial conjugation can overcome the immunosuppressive tumor microenvironment.
• This strategy holds potential for enhancing adoptive cell therapy efficacy in challenging cancer types.