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Chimeric antigen receptor macrophage therapy for breast tumours mediated by targeting the tumour extracellular matrix.
- Source :
-
British journal of cancer [Br J Cancer] 2019 Nov; Vol. 121 (10), pp. 837-845. Date of Electronic Publication: 2019 Oct 01. - Publication Year :
- 2019
-
Abstract
- Background: The extracellular matrix (ECM) is essential for malignant tumour progression, as it is a physical barrier to various kinds of anticancer therapies. Matrix metalloproteinase (MMPs) can degrade almost all ECM components, and macrophages are an important source of MMPs. Studies using macrophages to treat tumours have shown that macrophages can enter tumour tissue to play a regulatory role.<br />Methods: We modified macrophages with a designed chimeric antigen receptor (CAR), which could be activated after recognition of the tumour antigen HER2 to trigger the internal signalling of CD147 and increase the expression of MMPs.<br />Results: Although CAR-147 macrophage treatment did not affect tumour cell growth in vitro compared with control treatment. However, we found that the infusion of CAR-147 macrophages significantly inhibited HER2-4T1 tumour growth in BALB/c mice. Further investigation showed that CAR-147 macrophages could reduce tumour collagen deposition and promote T-cell infiltration into tumours, which were consistent with expectations. Interestingly, the levels of the inflammatory cytokines TNF-α and IL-6, which are key factors in cytokine release syndrome, were significantly decreased in the peripheral blood in CAR-147 macrophage-transfused mice.<br />Conclusion: Our data suggest that targeting the ECM by engineered macrophages would be an effective treatment strategy for solid tumours.
- Subjects :
- Animals
Breast Neoplasms genetics
Breast Neoplasms pathology
Cell Line, Tumor
Cell Proliferation drug effects
Collagen genetics
Extracellular Matrix genetics
Female
Heterografts
Humans
Lymphocytes, Tumor-Infiltrating drug effects
Lymphocytes, Tumor-Infiltrating metabolism
Macrophages metabolism
Macrophages transplantation
Matrix Metalloproteinases genetics
Mice
Receptors, Chimeric Antigen therapeutic use
Signal Transduction genetics
Tumor Necrosis Factor-alpha genetics
Breast Neoplasms therapy
Immunotherapy, Adoptive
Receptor, ErbB-2 genetics
Receptors, Chimeric Antigen genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1532-1827
- Volume :
- 121
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- British journal of cancer
- Publication Type :
- Academic Journal
- Accession number :
- 31570753
- Full Text :
- https://doi.org/10.1038/s41416-019-0578-3