CAR-macrophage: An extensive immune enhancer to fight cancer

Wang, Shuhang; Yang, Yuqi; Ma, Peiwen; Zha, Yan; Zhang, Jin; Lei, Anhua; Li, Ning

doi:10.1016/j.ebiom.2022.103873

Cited by 73 publications

(45 citation statements)

References 5 publications

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“…Macrophages perform multiple functions, including phagocytosis, immunomodulation, TME remodeling, and antigen-presenting. CAR-M-targeting-HER2 has specific phagocytosis capacity in vitro and murine breast cancer models whose immunosuppressive microenvironment could be improved in a HER2-dependent way [ 27 , 50 ]. CAR-NKs potentially eliminate tumor cells via NCRs, NKG2D, DNAM-1 (CD226) and certain activating KIRs (KIR2DS1, KIR2DS4, and KIR2DL4) independent of CAR, as well as through CD16-mediated antibody-dependent cell-mediated cytotoxicity (ADCC) [ 51 ].…”

Section: A Brief 40-year History Of Actmentioning

confidence: 99%

Adoptive cellular immunotherapy for solid neoplasms beyond CAR-T

Liu

Zheng

et al. 2023

Mol Cancer

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In recent decades, immune checkpoint blockade and chimeric antigen receptor T cell (CAR-T) therapy are two milestone achievements in clinical immunotherapy. However, both show limited efficacies in most solid neoplasms, which necessitates the exploration of new immunotherapeutic modalities. The failure of CAR-T and immune checkpoint blockade in several solid neoplasms is attributed to multiple factors, including low antigenicity of tumor cells, low infiltration of effector T cells, and diverse mechanisms of immunosuppression in the tumor microenvironment. New adoptive cell therapies have been attempted for solid neoplasms, including TCR-T, CAR-natural killer cells (CAR-NK), and CAR-macrophages (CAR-M). Compared to CAR-T, these new adoptive cell therapies have certain advantages in treating solid neoplasms. In this review, we summarized the 40-year evolution of adoptive cell therapies, then focused on the advances of TCR-T, CAR-NK, and CAR-M in solid neoplasms and discussed their potential clinical applications.

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Section: A Brief 40-year History Of Actmentioning

confidence: 99%

Adoptive cellular immunotherapy for solid neoplasms beyond CAR-T

Liu

Zheng

et al. 2023

Mol Cancer

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“…Nevertheless, due to the heterogeneity of liver cancer, exploring liver tumor cell-specific targets and engineering macrophages in liver TME remains challenging. It is also necessary to pay attention to the therapy's potential off-target toxicity and immunogenicity [180][181][182]. If the results of associated studies are to be translated into clinical practice, safer, more reliable and efficient CAR-M technologies should be developed.…”

Section: 21mentioning

confidence: 99%

Tumor‐associated macrophages in liver cancer: From mechanisms to therapy

Kun

Cai

Zhu

et al. 2022

Cancer Communications

172

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Multidimensional analyses have demonstrated the presence of a unique tumor microenvironment (TME) in liver cancer. Tumor‐associated macrophages (TAMs) are among the most abundant immune cells infiltrating the TME and are present at all stages of liver cancer progression, and targeting TAMs has become one of the most favored immunotherapy strategies. In addition, macrophages and liver cancer cells have distinct origins. At the early stage of liver cancer, macrophages can provide a niche for the maintenance of liver cancer stem cells. In contrast, cancer stem cells (CSCs) or poorly differentiated tumor cells are key factors modulating macrophage activation. In the present review, we first propose the origin connection between precursor macrophages and liver cancer cells. Macrophages undergo dynamic phenotypic transition during carcinogenesis. In this course of such transition, it is critical to determine the appropriate timing for therapy and block specific markers to suppress pro‐tumoral TAMs. The present review provides a more detailed discussion of transition trends of such surface markers than previous reviews. Complex crosstalk occurs between TAMs and liver cancer cells. TAMs play indispensable roles in tumor progression, angiogenesis, and autophagy due to their heterogeneity and robust plasticity. In addition, macrophages in the TME interact with other immune cells by directing cell‐to‐cell contact or secreting various effector molecules. Similarly, tumor cells combined with other immune cells can drive macrophage recruitment and polarization. Despite the latest achievements and the advancements in treatment strategies following TAMs studies, comprehensive discussions on the communication between macrophages and cancer cells or immune cells in liver cancer are currently lacking. In this review, we discussed the interactions between TAMs and liver cancer cells (from cell origin to maturation), the latest therapeutic strategies (including chimeric antigen receptor macrophages), and critical clinical trials for hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) to provide a rationale for further clinical investigation of TAMs as a potential target for treating patients with liver cancer.

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“…Generally, T cells are used as a host for the CAR to generate a robust T-cell response. Similar to T-cell CARs, Macrophage CARs consist of an extracellular domain for specific antigen recognition, a hinge domain, a transmembrane domain of CD8α and an intracellular domain of FCER1G, MEGF10, MERTK or CD3ζ molecules for downstream signaling [ 168 ]. Binding to the CAR induces phagocytosis of the cancer cells with the specific antigen, which is subsequently presented to T cells to initiate anti-cancer immunity [ 169 ].…”

Section: Immunotherapy Targeting Tamsmentioning

confidence: 99%

“…Momentarily, the second generation of CAR macrophages is being developed that focuses on the improvement of T-cell activation and antigen presentation. Additionally, special attention is being paid to potentiating the anti-cancer phenotype of the CAR macrophages [ 168 , 170 ]. Presently, a first in human clinical trial is investigating the therapeutic potential of CT-0508, autologous second-generation macrophages expressing an anti-HER2 CAR, in metastatic solid cancers (NCT04660929).…”

Section: Immunotherapy Targeting Tamsmentioning

confidence: 99%

The Interface of Tumour-Associated Macrophages with Dying Cancer Cells in Immuno-Oncology

Vanmeerbeek

Govaerts

Laureano

et al. 2022

Cells

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Tumour-associated macrophages (TAMs) are essential players in the tumour microenvironment (TME) and modulate various pro-tumorigenic functions such as immunosuppression, angiogenesis, cancer cell proliferation, invasion and metastasis, along with resistance to anti-cancer therapies. TAMs also mediate important anti-tumour functions and can clear dying cancer cells via efferocytosis. Thus, not surprisingly, TAMs exhibit heterogeneous activities and functional plasticity depending on the type and context of cancer cell death that they are faced with. This ultimately governs both the pro-tumorigenic and anti-tumorigenic activity of TAMs, making the interface between TAMs and dying cancer cells very important for modulating cancer growth and the efficacy of chemo-radiotherapy or immunotherapy. In this review, we discuss the interface of TAMs with cancer cell death from the perspectives of cell death pathways, TME-driven variations, TAM heterogeneity and cell-death-inducing anti-cancer therapies. We believe that a better understanding of how dying cancer cells influence TAMs can lead to improved combinatorial anti-cancer therapies, especially in combination with TAM-targeting immunotherapies.

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CAR-macrophage: An extensive immune enhancer to fight cancer

Cited by 73 publications

References 5 publications

Adoptive cellular immunotherapy for solid neoplasms beyond CAR-T

Adoptive cellular immunotherapy for solid neoplasms beyond CAR-T

Tumor‐associated macrophages in liver cancer: From mechanisms to therapy

The Interface of Tumour-Associated Macrophages with Dying Cancer Cells in Immuno-Oncology

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