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Author Spotlight: Creating Human Vascularized Micro-Tumors as Models for Translational Cancer Research
Published on: September 15, 2023
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Patient-Specific Vascularized Tumor Model: Blocking TAM Recruitment with Multispecific Antibodies Targeting CCR2 and
Huu Tuan Nguyen1, Nadia Gurvich2, Mark Robert Gillrie1,3
1Department of Mechanical Engineering and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139 USA.
Biorxiv : the Preprint Server for Biology
|December 11, 2023
Summary
Tumor-associated macrophages (TAMs) promote cancer. A new 3D model using human monocytes and vascular networks effectively models TAMs and tests therapies, showing promise for new cancer treatments.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Tumor-associated inflammation, driven by tumor-associated macrophages (TAMs), fuels cancer progression and resistance to therapy.
- TAM infiltration correlates with poor prognosis across various cancers, highlighting TAMs as therapeutic targets.
Approach:
- Developed a novel in vitro 3D vascularized tumor model using human monocytes, tumor spheroids, and patient tissues.
- Investigated monocyte trafficking into tumors and evaluated immunotherapies within this humanized tumor microenvironment.
- Assessed a multispecific antibody (CSF1R/CCR2/TGF-β Ab) for its ability to modulate monocyte and macrophage behavior.
Key Points:
- Macrophages in vascularized tumor models enhance monocyte recruitment via TAM-secreted CCL7 and CCL2, mediated by CSF-1R.
- The CSF1R/CCR2/TGF-β antibody effectively repolarizes TAMs to an anti-tumoral M1-like phenotype.
- This antibody reduces chemoattractant secretion, blocks monocyte migration, and inhibits recruitment in patient-specific models.
Conclusions:
- The developed 3D vascularized tumor model provides crucial insights into monocyte recruitment dynamics.
- This model enables functional evaluation of novel therapeutic antibodies targeting TAMs in the tumor microenvironment.
- Findings support the potential of targeting TAMs and CSF-1R/CCR2/TGF-β pathways for cancer immunotherapy.
