Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 121 (10), 837-845

Chimeric Antigen Receptor Macrophage Therapy for Breast Tumours Mediated by Targeting the Tumour Extracellular Matrix


Chimeric Antigen Receptor Macrophage Therapy for Breast Tumours Mediated by Targeting the Tumour Extracellular Matrix

Wenlong Zhang et al. Br J Cancer.


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.

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.

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.

Conclusion: Our data suggest that targeting the ECM by engineered macrophages would be an effective treatment strategy for solid tumours.

Conflict of interest statement

The authors declare no competing interests.

Similar articles

See all similar articles


    1. Vesely MD, Kershaw MH, Schreiber RD, Smyth MJ. Natural innate and adaptive immunity to cancer. Annu. Rev. Immunol. 2011;29:235–271. doi: 10.1146/annurev-immunol-031210-101324. - DOI - PubMed
    1. Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science. 2011;331:1565–1570. doi: 10.1126/science.1203486. - DOI - PubMed
    1. Gross G, Waks T, Eshhar Z. Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity. Proc. Natl Acad. Sci. USA. 1989;86:10024–10028. doi: 10.1073/pnas.86.24.10024. - DOI - PMC - PubMed
    1. D’Aloia MM, Zizzari IG, Sacchetti B, Pierelli L, Alimandi M. CAR-T cells: the long and winding road to solid tumors. Cell Death Dis. 2018;9:282. doi: 10.1038/s41419-018-0278-6. - DOI - PMC - PubMed
    1. Gajewski TF, Schreiber H, Fu YX. Innate and adaptive immune cells in the tumor microenvironment. Nat. Immunol. 2013;14:1014–1022. doi: 10.1038/ni.2703. - DOI - PMC - PubMed