Antibody-secreting macrophages generated using CpG-free plasmid eliminate tumor cells through antibody-dependent cellular phagocytosis

Bi, Eun; Shin, Kyung‐Hwa; Seo, Jinho; Oh, Doo-Byoung

doi:10.5483/bmbrep.2020.53.8.024

Cited by 9 publications

(9 citation statements)

References 32 publications

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“…In addition, Ad5f35 infected macrophages activate the inflammasome and participate in maintaining the M1 phenotype generated by proinflammatory priming signals [ 235 ]. Additionally, transposon systems, mRNA transfection and bacterial plasmid DNA, have also been used as non-viral strategies for macrophages bioengineering [ 236 – 238 ]. Moreover, using polymer nanocarriers (mannose-conjugated polyethyleneimine (MPEI)), Kang and colleagues, were able to transfer the genes encoding CAR and IFN-γ into macrophages to enhance their anti-tumor potential [ 226 ].…”

Section: Car-m Cell Therapy In Solid Tumors: Applications Challenges ...mentioning

confidence: 99%

CAR-cell therapy in the era of solid tumor treatment: current challenges and emerging therapeutic advances

et al. 2023

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In the last decade, Chimeric Antigen Receptor (CAR)-T cell therapy has emerged as a promising immunotherapeutic approach to fight cancers. This approach consists of genetically engineered immune cells expressing a surface receptor, called CAR, that specifically targets antigens expressed on the surface of tumor cells. In hematological malignancies like leukemias, myeloma, and non-Hodgkin B-cell lymphomas, adoptive CAR-T cell therapy has shown efficacy in treating chemotherapy refractory patients. However, the value of this therapy remains inconclusive in the context of solid tumors and is restrained by several obstacles including limited tumor trafficking and infiltration, the presence of an immunosuppressive tumor microenvironment, as well as adverse events associated with such therapy. Recently, CAR-Natural Killer (CAR-NK) and CAR-macrophages (CAR-M) were introduced as a complement/alternative to CAR-T cell therapy for solid tumors. CAR-NK cells could be a favorable substitute for CAR-T cells since they do not require HLA compatibility and have limited toxicity. Additionally, CAR-NK cells might be generated in large scale from several sources which would suggest them as promising off-the-shelf product. CAR-M immunotherapy with its capabilities of phagocytosis, tumor-antigen presentation, and broad tumor infiltration, is currently being investigated. Here, we discuss the emerging role of CAR-T, CAR-NK, and CAR-M cells in solid tumors. We also highlight the advantages and drawbacks of CAR-NK and CAR-M cells compared to CAR-T cells. Finally, we suggest prospective solutions such as potential combination therapies to enhance the efficacy of CAR-cells immunotherapy.

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Section: Car-m Cell Therapy In Solid Tumors: Applications Challenges ...mentioning

confidence: 99%

CAR-cell therapy in the era of solid tumor treatment: current challenges and emerging therapeutic advances

et al. 2023

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“…Recent approaches have used genetic engineering to design macrophages that express proinflammatory transgenes of interest (12,(44)(45)(46)(47)(48)(49). These strategies leverage the tumor-homing tendences of macrophages to locally deliver therapeutic cargo and induce cytotoxic activity within the tumor niche.…”

Section: Reprogramming Macrophages For Tumor Suppression With Cellular Engineeringmentioning

confidence: 99%

“…BiTE-secreting GEMs facilitated antigen-specific killing by T cells, which was further augmented by the groups work on IL-12 GEMs (44). Cha et al similarly targeted EGFR by encoding a secreted single-chain variable fragment (scFv) fused to a Fc moiety, which opsonized tumor cells and induced antibody-dependent cellular phagocytosis (ADCP) by macrophages (49). Notably, engineered macrophages can deliver cargo other than genetically encoded proteins; for example, Huang and colleagues used nanoparticles to engineer macrophages that carry photo-sensitive cytotoxic agents, which are released and induce immunogenic cell death upon exposure to near infrared light (51).…”

Section: Reprogramming Macrophages For Tumor Suppression With Cellular Engineeringmentioning

confidence: 99%

“…The bacterial origin of plasmid DNA can contribute to inflammation and gene silencing. Plasmids devoid of unmethylated cytosine-phospho-guanine (CpG) dinucleotides – a signature of bacterial DNA – were shown to evade detection by TLR9 and exhibit prolonged gene expression in RAW 264.7 macrophages and primary murine BMDMs ( 49 ). Other work has optimized the transient delivery of mRNA to monocytes and macrophages, carefully selecting mRNA modifications and transfection reagents to minimize transfection-induced macrophage toxicity or activation ( 84 , 85 ).…”

Section: Car-m: Macrophages Take the Wheelmentioning

confidence: 99%

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Engineered CAR-Macrophages as Adoptive Immunotherapies for Solid Tumors

2021

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Cellular immunotherapies represent a promising approach for the treatment of cancer. Engineered adoptive cell therapies redirect and augment a leukocyte’s inherent ability to mount an immune response by introducing novel anti-tumor capabilities and targeting moieties. A prominent example of this approach is the use of T cells engineered to express chimeric antigen receptors (CARs), which have demonstrated significant efficacy against some hematologic malignancies. Despite increasingly sophisticated strategies to harness immune cell function, efficacy against solid tumors has remained elusive for adoptive cell therapies. Amongst cell types used in immunotherapies, however, macrophages have recently emerged as prominent candidates for the treatment of solid tumors. In this review, we discuss the use of monocytes and macrophages as adoptive cell therapies. Macrophages are innate immune cells that are intrinsically equipped with broad therapeutic effector functions, including active trafficking to tumor sites, direct tumor phagocytosis, activation of the tumor microenvironment and professional antigen presentation. We focus on engineering strategies for manipulating macrophages, with a specific focus on CAR macrophages (CAR-M). We highlight CAR design for macrophages, the production of CAR-M for adoptive cell transfer, and clinical considerations for their use in treating solid malignancies. We then outline recent progress and results in applying CAR-M as immunotherapies. The recent development of engineered macrophage-based therapies holds promise as a key weapon in the immune cell therapy armamentarium.

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“…This process is known as ADCP. 83 In order to further extend the mechanism of action to recruit and activate bystander immune cells to further improve the antitumor immune response, Gardell and her group engineered human macrophages to secrete a BiTE, which resulted in antigen-dependent T cell responses in a glioblastoma xenograft model. 84 In addition, the BiTE-secreting macrophages were equipped with IL-12, which led to increased reduction of tumor burden in both subcutaneous and intracranial mouse glioblastoma models.…”

Section: Alternative Engineering and Molecular Reprograming Of Macrophages Into Potent Cancer Eradicating Cellsmentioning

confidence: 99%

CARs and beyond: tailoring macrophage-based cell therapeutics to combat solid malignancies

Abdin

Paasch

Morgan

et al. 2021

J Immunother Cancer

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Recent understanding of the role and contribution of immune cells in disease onset and progression has pioneered the field of immunotherapies. Use of genetic engineering to deliver, correct or enhance immune cells has been clinically successful, especially in the field of cancer immunotherapy. Indeed, one of the most attractive approaches is the introduction of chimeric antigen receptors (CARs) to immune cells, such as T cells. Recent studies revealed that adapting this platform for use in macrophages may widen the spectrum of CAR applications for better control of solid tumors and, thus, extend this treatment strategy to more patients with cancer. Given the novel insights into tumor-associated macrophages and new targeting strategies to boost anticancer therapy, this review aims to provide an overview of the current status of the role of macrophages in cancer therapy. The various genetic engineering approaches that can be used to optimize macrophages for use in oncology are discussed, with special attention dedicated to the implication of the CAR platform on macrophages for anticancer therapy. The current clinical status, challenges and future perspective of macrophage-based drugs are highlighted.

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Antibody-secreting macrophages generated using CpG-free plasmid eliminate tumor cells through antibody-dependent cellular phagocytosis

Cited by 9 publications

References 32 publications

CAR-cell therapy in the era of solid tumor treatment: current challenges and emerging therapeutic advances

CAR-cell therapy in the era of solid tumor treatment: current challenges and emerging therapeutic advances

Engineered CAR-Macrophages as Adoptive Immunotherapies for Solid Tumors

CARs and beyond: tailoring macrophage-based cell therapeutics to combat solid malignancies

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