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Updated: Jul 8, 2025
Author Spotlight: Creating Human Vascularized Micro-Tumors as Models for Translational Cancer Research
Published on: September 15, 2023
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.
Abstract:
Tumor-associated inflammation drives cancer progression and therapy resistance, with the infiltration of monocyte-derived tumor-associated macrophages (TAMs) associated with poor prognosis in diverse cancers. Targeting TAMs holds potential against solid tumors, but effective immunotherapies require testing on immunocompetent human models prior to clinical trials. Here, we develop an in vitro model of microvascular networks that incorporates tumor spheroids or patient tissues. By perfusing the vasculature with human monocytes, we investigate monocyte trafficking into the tumor and evaluate immunotherapies targeting the human tumor microenvironment. Our findings demonstrate that macrophages in vascularized breast and lung tumor models can enhance monocyte recruitment via TAM-produced CCL7 and CCL2, mediated by CSF-1R. Additionally, we assess a novel multispecific antibody targeting CCR2, CSF-1R, and neutralizing TGF-β, referred to as CSF1R/CCR2/TGF-β Ab, on monocytes and macrophages using our 3D models. This antibody repolarizes TAMs towards an anti-tumoral M1-like phenotype, reduces monocyte chemoattractant protein secretion, and effectively blocks monocyte migration. Finally, we show that the CSF1R/CCR2/TGF-β Ab inhibits monocyte recruitment in patient-specific vascularized tumor models. Overall, this vascularized tumor model offers valuable insights into monocyte recruitment and enables functional testing of innovative therapeutic antibodies targeting TAMs in the tumor microenvironment (TME).
Insights
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.
