scholarly journals Engineering Macrophages via Nanotechnology and Genetic Manipulation for Cancer Therapy

2022 ◽  
Vol 11 ◽  
Author(s):  
Xiaoling Ding ◽  
Xinchen Sun ◽  
Huihui Cai ◽  
Lei Wu ◽  
Ying Liu ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Therapy ◽  
Genetic Manipulation ◽  
Dependent Manner ◽  
Antigen Receptors ◽  
Chimeric Antigen Receptors ◽  
Macrophage Cell ◽  
Drug Nanoparticles ◽  
Anticancer Effects ◽  
New Directions

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.

Redirection of T-cell effector functions for cancer therapy: bispecific antibodies and chimeric antigen receptors

2013 ◽  
Vol 9 (4) ◽  
pp. 527-539 ◽  
Author(s):  
Alessandro Satta ◽  
Delia Mezzanzanica ◽  
Fabio Turatti ◽  
Silvana Canevari ◽  
Mariangela Figini
Keyword(s):  
T Cell ◽  
Cancer Therapy ◽  
Bispecific Antibodies ◽  
Antigen Receptors ◽  
Chimeric Antigen Receptors ◽  
Effector Functions ◽  
Cell Effector

scholarly journals Atom-Precise Fluorescent Copper Cluster for Tumor Microenvironment Targeting and Transient Chemodynamic Cancer Therapy

2021 ◽  
Author(s):  
Zhenzhen Yang ◽  
Anli Yang ◽  
Wang Ma ◽  
Kai Ma ◽  
Ya-Kun Lv ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Therapy ◽  
Dependent Manner ◽  
Metal Nanoclusters ◽  
Concentration Dependent Manner ◽  
In Vivo Experiments ◽  
Low Cytotoxicity ◽  
High Cytotoxicity

Abstract Background: Reactive oxygen species (ROS) have been widely studied for cancer therapy. Nevertheless, instability and aspecific damages to cellular biomolecules limited the application effect. Recently, significant research efforts have been witnessed in the flourishing area of metal nanoclusters (NCs) with atomically precise structures for targeted release of ROS but few achieved success towards targeting tumor microenvironment.Results: In this work, we reported an atomically precise nanocluster Cu6(C4H3N2S)6 (Cu6NC), which could slowly break and generate ROS once encountered with acidic. The as-prepared Cu6NC demonstrated high biological safety and efficient chemodynamic anti-tumor properties. Moreover, Cu6NC enabled transient release of ROS and contained targeting behavior led by the tumor microenvironment. Both in vitro and in vivo experiments confirmed that Cu6NC demonstrated a low cytotoxicity for normal cells, while presented high cytotoxicity for tumor cells with a concentration-dependent manner.Conclusions: This work not only reported a promising candidate for chemodynamic cancer therapy, but also paved the route to address clinical issues at the atomic level.

scholarly journals Preclinical Evaluation of Invariant Natural Killer T Cells Modified with CD38 or BCMA Chimeric Antigen Receptors for Multiple Myeloma

2021 ◽  
Vol 22 (3) ◽  
pp. 1096
Author(s):  
Renée Poels ◽  
Esther Drent ◽  
Roeland Lameris ◽  
Afroditi Katsarou ◽  
Maria Themeli ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Natural Killer ◽  
Therapeutic Potential ◽  
Cytotoxic Activities ◽  
Dependent Manner ◽  
Antigen Receptors ◽  
Inkt Cells ◽  
Chimeric Antigen Receptors ◽  
Invariant Natural Killer ◽  
Natural Killer T

Due to the CD1d restricted recognition of altered glycolipids, Vα24-invariant natural killer T (iNKT) cells are excellent tools for cancer immunotherapy with a significantly reduced risk for graft-versus-host disease when applied as off-the shelf-therapeutics across Human Leukocyte Antigen (HLA) barriers. To maximally harness their therapeutic potential for multiple myeloma (MM) treatment, we here armed iNKT cells with chimeric antigen receptors (CAR) directed against the MM-associated antigen CD38 and the plasma cell specific B cell maturation antigen (BCMA). We demonstrate that both CD38- and BCMA-CAR iNKT cells effectively eliminated MM cells in a CAR-dependent manner, without losing their T cell receptor (TCR)-mediated cytotoxic activity. Importantly, iNKT cells expressing either BCMA-CARs or affinity-optimized CD38-CARs spared normal hematopoietic cells and displayed a Th1-like cytokine profile, indicating their therapeutic utility. While the costimulatory domain of CD38-CARs had no influence on the cytotoxic functions of iNKT cells, CARs containing the 4-1BB domain showed a better expansion capacity. Interestingly, when stimulated only via CD1d+ dendritic cells (DCs) loaded with α-galactosylceramide (α-GalCer), both CD38- and BCMA-CAR iNKT cells expanded well, without losing their CAR- or TCR-dependent cytotoxic activities. This suggests the possibility of developing an off-the-shelf therapy with CAR iNKT cells, which might even be boostable in vivo by administration α-GalCer pulsed DCs.

Modulation of MicroRNAs by Euphorbia Microsciadia Boiss in MDA-MB-231 Cell Line: New Possibilities in Breast Cancer Therapy

2020 ◽  
Vol 15 (2) ◽  
pp. 174-184 ◽  
Author(s):  
Mohammad-Reza Mahmoudian-Sani ◽  
Majid Asadi-Samani
Keyword(s):  
Breast Cancer ◽  
Cancer Therapy ◽  
Cell Line ◽  
Dependent Manner ◽  
Breast Cancer Therapy ◽  
Cytotoxic Effects ◽  
Hydroalcoholic Extract ◽  
Cycle Arrest ◽  
Anticancer Effects ◽  
Dose Dependent

Background: A large number of Euphorbia species have been evaluated for anticancer effects; however, their anticancer mechanisms have not been established up to now. Objective: : The present study aimed to evaluate the effects of Euphorbia microsciadia (E. microsciadia) Boiss on the modulation of micro (mi) RNAs in MDA-MB-231 cell line. Methods: As the first step, the inhibitory concentration of hydroalcoholic extract of E. microsciadia on MDA-MB-231 cells was examined using the MTT assay, bypassing 24 and 48h from seeding. The real-time quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) was also utilized to determine Let-7, miR-15, miR-16, miR-29, miR-151, miR-155, miR-21, miR-146b, miR-181b, miR-221, miR-222, miR-21, and miR-146b expressions in MDA-MB-231 cells, by passing 24 and 48h from treating with the extract of E. microsciadia. Results: The results reveal the cytotoxic effects of E. microsciadia on MDA-MB-231 cell line in a dose-dependent manner. The half maximal Inhibitory Concentrations (IC50) were also equal to 275 and 240μg/ml for E. microsciadia, by passing 24 and 48h from the treatment, respectively. Furthermore, it was confirmed that, E. microsciadia had augmented the expression levels of Let-7, miR-15, miR-16, miR-29, and miR-34a, which lead to an increase in apoptosis. Conclusion: E. microsciadia could modulate some miRNAs involved in cell cycle arrest and apoptosis in MDA-MB-231 cell line. Accordingly, targeting miRNAs by E. microsciadia can open some newer avenues for breast cancer therapy.

scholarly journals Atom-precise fluorescent copper cluster for tumor microenvironment targeting and transient chemodynamic cancer therapy

2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Zhenzhen Yang ◽  
Anli Yang ◽  
Wang Ma ◽  
Kai Ma ◽  
Ya-Kun Lv ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Therapy ◽  
Dependent Manner ◽  
Metal Nanoclusters ◽  
Concentration Dependent Manner ◽  
In Vivo Experiments ◽  
Low Cytotoxicity ◽  
High Cytotoxicity

Abstract Background Reactive oxygen species (ROS) have been widely studied for cancer therapy. Nevertheless, instability and aspecific damages to cellular biomolecules limit the application effect. Recently, significant research efforts have been witnessed in the flourishing area of metal nanoclusters (NCs) with atomically precise structures for targeted release of ROS but few achieved success towards targeting tumor microenvironment. Results In this work, we reported an atomically precise nanocluster Cu6(C4H3N2S)6 (Cu6NC), which could slowly break and generate ROS once encountered with acidic. The as-prepared Cu6NC demonstrated high biological safety and efficient chemodynamic anti-tumor properties. Moreover, Cu6NC enabled transient release of ROS and contained targeting behavior led by the tumor microenvironment. Both in vitro and in vivo experiments confirmed that Cu6NC demonstrated a low cytotoxicity for normal cells, while presented high cytotoxicity for tumor cells with a concentration-dependent manner. Conclusions This work not only reported a promising candidate for chemodynamic cancer therapy, but also paved the route to address clinical issues at the atomic level. Graphical Abstract

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