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Patient-specific vascularized tumor model: Blocking monocyte recruitment with multispecific antibodies targeting CCR2 and CSF-1R.
Nguyen, Huu Tuan; Kan, Ellen L; Humayun, Mouhita; Gurvich, Nadia; Offeddu, Giovanni S; Wan, Zhengpeng; Coughlin, Mark F; Renteria, Diana C; Loew, Andreas; Wilson, Susan; Zhang, Christie; Vu, Vivian; Lee, Sharon Wei Ling; Tan, Seng-Lai; Barbie, David; Hsu, Jonathan; Gillrie, Mark Robert; Kamm, Roger D.
Afiliación
  • Nguyen HT; Department of Mechanical Engineering and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA. Electronic address: htn@mit.edu.
  • Kan EL; Department of Mechanical Engineering and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Humayun M; Department of Mechanical Engineering and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Gurvich N; Marengo Therapeutics, 840 Memorial Dr, Cambridge, MA, 02139, USA.
  • Offeddu GS; Department of Mechanical Engineering and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Wan Z; Department of Mechanical Engineering and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Coughlin MF; Department of Mechanical Engineering and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Renteria DC; Department of Mechanical Engineering and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Loew A; Marengo Therapeutics, 840 Memorial Dr, Cambridge, MA, 02139, USA.
  • Wilson S; Marengo Therapeutics, 840 Memorial Dr, Cambridge, MA, 02139, USA.
  • Zhang C; Marengo Therapeutics, 840 Memorial Dr, Cambridge, MA, 02139, USA.
  • Vu V; Department of Mechanical Engineering and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Lee SWL; Department of Mechanical Engineering and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Tan SL; Marengo Therapeutics, 840 Memorial Dr, Cambridge, MA, 02139, USA.
  • Barbie D; Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA; Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Hsu J; Marengo Therapeutics, 840 Memorial Dr, Cambridge, MA, 02139, USA.
  • Gillrie MR; Department of Mechanical Engineering and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA; Department of Medicine, University of Calgary, Calgary, AB, T2N 1N4, Canada. Electronic address: mark.gillrie@ucalgary.ca.
  • Kamm RD; Department of Mechanical Engineering and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA. Electronic address: rdkamm@mit.edu.
Biomaterials ; 312: 122731, 2025 Jan.
Article en En | MEDLINE | ID: mdl-39153324
ABSTRACT
Tumor-associated inflammation drives cancer progression and therapy resistance, often linked to the infiltration of monocyte-derived tumor-associated macrophages (TAMs), which are associated with poor prognosis in various cancers. To advance immunotherapies, testing on immunocompetent pre-clinical models of human tissue is crucial. We have developed an in vitro model of microvascular networks with tumor spheroids or patient tissues to assess monocyte trafficking into tumors 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 CCL7 and CCL2, mediated by CSF-1R. Additionally, a multispecific antibody targeting CSF-1R, CCR2, and neutralizing TGF-ß (CSF1R/CCR2/TGF-ß Ab) repolarizes TAMs towards an anti-tumoral M1-like phenotype, reduces monocyte chemoattractant protein secretion, and blocks monocyte migration. This antibody also inhibits monocyte recruitment in patient-specific vascularized tumor models. In summary, this vascularized tumor model recapitulates the monocyte recruitment cascade, enabling functional testing of innovative therapeutic antibodies targeting TAMs in the tumor microenvironment.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Monocitos / Receptor de Factor Estimulante de Colonias de Macrófagos / Receptores CCR2 / Microambiente Tumoral Límite: Animals / Female / Humans Idioma: En Revista: Biomaterials Año: 2025 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Monocitos / Receptor de Factor Estimulante de Colonias de Macrófagos / Receptores CCR2 / Microambiente Tumoral Límite: Animals / Female / Humans Idioma: En Revista: Biomaterials Año: 2025 Tipo del documento: Article Pais de publicación: Países Bajos