Living Leukocyte‐Based Drug Delivery Systems

Advanced Materials, Journal Year: 2022, Volume and Issue: 35(17)

Published: Nov. 1, 2022

Abstract Leukocytes play a vital role in immune responses, including defending against invasive pathogens, reconstructing impaired tissue, and maintaining homeostasis. When the system is activated vivo, leukocytes accomplish series of orderly complex regulatory processes. While cancer inflammation‐related diseases like sepsis are critical medical difficulties plaguing humankind around world, have been shown to largely gather at focal site, significantly contribute inflammation progression. Therefore, living leukocyte‐based drug delivery systems attracted considerable attention recent years due innate specific targeting effect, low immunogenicity, improved therapeutic efficacy, reverse effect. In this review, advances development macrophages, neutrophils, lymphocytes as promising treatment strategies for introduced. The advantages, current challenges, limitations these also discussed, well perspectives on future precision targeted therapy clinics provided. Collectively, it expected that such kind cell‐based improve or even revolutionize treatments cancers clinics.

Language: Английский

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CAR-Macrophages and CAR-T Cells Synergistically Kill Tumor Cells In Vitro

Cells, Journal Year: 2022, Volume and Issue: 11(22), P. 3692 - 3692

Published: Nov. 21, 2022

Chimeric antigen receptor (CAR)-expressing macrophages (CAR-M) have a great potential to improve cancer therapy, as shown from several recent preclinical studies. However, unlike CAR-T cell which has been widely studied, the efficacy and limitations of CAR-M cells remain be established. To address this issue, in present study, we compared three intracellular signaling domains (derived common γ subunit Fc receptors (FcRγ), multiple EGF-like-domains protein 10 (Megf10), CD19 cytoplasmic domain that recruits p85 phosphoinositide-3 kinase (PI3K), respectively) for their ability promote primary functions, investigated synergistic effect between kill tumor cells. We found CAR-MFcRγ exerted more potent phagocytic tumor-killing capacity than CAR-MMegf10 CAR-MPI3K. demonstrated cytotoxicity against vitro. Mechanistically, inflammatory factors secreted by increased expression costimulatory ligands (CD86 CD80) on augmented inducing macrophage M1 polarization. The upregulated may fitness activation turn, achieving significantly enhanced cytotoxicity. Taken together, our study first time could synergize with cells, provides proof-of-concept novel combinational immunotherapy.

Language: Английский

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Targeting macrophages: a novel treatment strategy in solid tumors

Journal of Translational Medicine, Journal Year: 2022, Volume and Issue: 20(1)

Published: Dec. 12, 2022

In the tumor microenvironment (TME), tumor-associated macrophages (TAMs) are most abundant immune cells, which act as a key regulator in tumorigenesis and progression. Increasing evidence have demonstrated that TME alters nature of to maintain dynamic tissue homeostasis, allowing TAMs acquire ability stimulate angiogenesis, promote metastasis recurrence, suppress anti-tumor responses. Furthermore, tumors with high TAM infiltration poor prognoses resistant treatment. field solid tumor, exploration tumor-promoting mechanisms has attracted much attention targeting emerged promising immunotherapeutic strategy. Currently, common therapeutic options for follows: deletion TAMs, inhibition recruitment, release phagocytosis by reprogramming remodel their capacity. Promisingly, study chimeric antigen receptor (CAR-Ms) may provide even greater benefit patients tumors. this review, we discuss how progression well summarize emerging strategies macrophages.

Language: Английский

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Tumor-associated macrophage-related strategies for glioma immunotherapy

npj Precision Oncology, Journal Year: 2023, Volume and Issue: 7(1)

Published: Aug. 19, 2023

Abstract High-grade glioma is one of the deadliest primary tumors central nervous system. Despite many novel immunotherapies currently in development, it has been difficult to achieve breakthrough results clinical studies. The reason may be due suppressive tumor microenvironment gliomas that limits function specific immune cells (e.g., T cells) which are targets immunotherapy. However, tumor-associated macrophage, enriched tumors, plays an important role development GBM and becoming a research hotspot for This review focuses on current advances use macrophages as therapeutic or tools gliomas, provides some potential directions.

Language: Английский

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Hydrogel-enabled, local administration and combinatorial delivery of immunotherapies for cancer treatment

Materials Today, Journal Year: 2023, Volume and Issue: 65, P. 227 - 243

Published: March 31, 2023

Throughout the last decade, interventions to engineer immune system called immunotherapy have revolutionized fields of oncology and autoimmune disease. Researchers are developing platforms that enable new modes expand current limitations by incorporating non-intravenous delivery strategies. Recent advances in include use chemokines direct cells into tumors, alternative combinatorial therapies, oncolytic viruses. Similarly, there been significant breakthroughs design understanding biocompatible hydrogel-based materials for diverse biomedical applications, including large molecule drug delivery. In this review, we discuss how hydrogel can otherwise not feasible. Despite many pre-clinical successes hydrogels immunotherapies treatment cancer, still face challenges getting clinic eventually approved. Herein examine application high concentration subcutaneous, intratumoral, peritumoral, intraperitoneal, intracranial, pulmonary immunotherapies. By analyzing results hydrogel-enabled studies, describe local is a promising approach increase efficacy decrease systemic toxicities We also synergistic immunotherapy. Furthermore, summarize advancements obstacles intratumoral administration sustained release immunotherapy-loaded hydrogels. Finally, translational research, clinical development, manufacturing which must be addressed advance field.

Language: Английский

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