Engineered macrophages as near-infrared light activated drug vectors for chemo-photodynamic therapy of primary and bone metastatic breast cancer

Huang, Yanjuan; Guan, Zilin; Dai, Xiuling; Shen, Yifeng; Qin, Wei; Ren, Lingling; Jiang, Jingwen; Xiao, Zidong; Jiang, Yali; Liu, Di; Huang, Zeqian; Xu, Xiaoyu; Luo, Yong; Zhao, Chunshun

doi:10.1038/s41467-021-24564-0

Cited by 111 publications

(90 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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%

Engineered CAR-Macrophages as Adoptive Immunotherapies for Solid Tumors

2021

View full text Add to dashboard Cite

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.

show abstract

Section: Reprogramming Macrophages For Tumor Suppression With Cellular Engineeringmentioning

confidence: 99%

Engineered CAR-Macrophages as Adoptive Immunotherapies for Solid Tumors

2021

View full text Add to dashboard Cite

show abstract

“…One source is primary macrophages, such as bone marrow-derived macrophages, alveolar macrophages, and peritoneal macrophages. The second source is cell lines, including the mouse macrophage cell lines RAW264.7 and J774A.1 and the human peripheral blood monocyte cell line THP-1 (24,41,(88)(89)(90)(91). NPL-Ms can carry a variety of NPs, including liposomes (92,93), magnetic NPs (94,95), polymeric NPs (96,97), gold (AU) NPs (98)(99)(100)(101), and others (102,103).…”

Section: Engineering Macrophages For Np Delivery In Cancer Therapy Np Loading In Macrophagesmentioning

confidence: 99%

“…Many studies have demonstrated that NP-loaded macrophages (NPL-Ms) can directionally migrate to tumors and transport the payload to tumor cells, leading to a pronounced antitumor effect (39,40). Moreover, after reaching tumors, these engineered macrophages can exert additional effects by stimulating anticancer immune responses (24,41). In this review, we first introduce the origin, differentiation, and function of macrophages as well as the application of nanotechnology in anticancer therapy.…”

Section: Introductionmentioning

confidence: 99%

Engineering Macrophages via Nanotechnology and Genetic Manipulation for Cancer Therapy

et al. 2022

View full text Add to dashboard Cite

Macrophages play critical roles in tumor progression. In the tumor microenvironment, macrophages display highly diverse phenotypes and may perform antitumorigenic or protumorigenic functions in a context-dependent manner. Recent studies have shown that macrophages can be engineered to transport drug nanoparticles (NPs) to tumor sites in a targeted manner, thereby exerting significant anticancer effects. In addition, macrophages engineered to express chimeric antigen receptors (CARs) were shown to actively migrate to tumor sites and eliminate tumor cells through phagocytosis. Importantly, after reaching tumor sites, these engineered macrophages can significantly change the otherwise immune-suppressive tumor microenvironment and thereby enhance T cell-mediated anticancer immune responses. In this review, we first introduce the multifaceted activities of macrophages and the principles of nanotechnology in cancer therapy and then elaborate on macrophage engineering via nanotechnology or genetic approaches and discuss the effects, mechanisms, and limitations of such engineered macrophages, with a focus on using live macrophages as carriers to actively deliver NP drugs to tumor sites. Several new directions in macrophage engineering are reviewed, such as transporting NP drugs through macrophage cell membranes or extracellular vesicles, reprogramming tumor-associated macrophages (TAMs) by nanotechnology, and engineering macrophages with CARs. Finally, we discuss the possibility of combining engineered macrophages and other treatments to improve outcomes in cancer therapy.

show abstract

“…Then, the loaded drugs can be released in response to either endogenous or exogenous stimuli [89]. Cells that have been reported for use as nanomaterial carriers include stem cells [90], leukocytes [91], red blood cells [92], and T cells [93]. Methods of endogenous stimulation include pH, reactive oxygen species (ROS), enzyme, hypoxia and so on [94].…”

Section: Nature Cellmentioning

confidence: 99%

Optimization of Nanoparticles for Smart Drug Delivery: A Review

et al. 2021

View full text Add to dashboard Cite

Nanoparticle delivery systems have good application prospects in the treatment of various diseases, especially in cancer treatment. The effect of drug delivery is regulated by the properties of nanoparticles. There have been many studies focusing on optimizing the structure of nanoparticles in recent years, and a series of achievements have been made. This review summarizes the optimization strategies of nanoparticles from three aspects—improving biocompatibility, increasing the targeting efficiency of nanoparticles, and improving the drug loading rate of nanoparticles—aiming to provide some theoretical reference for the subsequent drug delivery of nanoparticles.

show abstract

Engineered macrophages as near-infrared light activated drug vectors for chemo-photodynamic therapy of primary and bone metastatic breast cancer

Cited by 111 publications

References 65 publications

Engineered CAR-Macrophages as Adoptive Immunotherapies for Solid Tumors

Engineered CAR-Macrophages as Adoptive Immunotherapies for Solid Tumors

Engineering Macrophages via Nanotechnology and Genetic Manipulation for Cancer Therapy

Optimization of Nanoparticles for Smart Drug Delivery: A Review

Contact Info

Product

Resources

About