Lipid nanoparticle‐mediated RNA delivery for immune cell modulation

European Journal of Immunology, Journal Year: 2024, Volume and Issue: 54(12)

Published: Sept. 16, 2024

Lipid nanoparticles (LNPs) have emerged as the preeminent nonviral drug delivery vehicles for nucleic acid therapeutics, exemplified by their usage in mRNA COVID-19 vaccines. As a safe and highly modular platform, LNPs are attractive wide range of applications. In addition to vaccines, being utilized platforms other immunoengineering efforts, especially cancer immunotherapies modulating immune cells functionality via delivery. this review, we focus on methods applications LNP-based immunotherapy five cell types: T cells, NK macrophages, stem dendritic cells. Each these types has wide-reaching but comes with unique challenges barriers. By combining knowledge immunology nanotechnology, can be developed improved targeting transfection, ultimately working toward novel clinical therapeutics.

Language: Английский

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Unlocking antitumor immunity with adenosine receptor blockers

Cancer Drug Resistance, Journal Year: 2023, Volume and Issue: 6(4), P. 748 - 67

Published: Oct. 23, 2023

Tumors survive by creating a tumor microenvironment (TME) that suppresses antitumor immunity. The TME the immune system limiting antigen presentation, inhibiting lymphocyte and natural killer (NK) cell activation, facilitating T exhaustion. Checkpoint inhibitors like anti-PD-1 anti-CTLA are immunostimulatory antibodies, their blockade extends survival of some but not all cancer patients. Extracellular adenosine triphosphate (ATP) is abundant in inflamed tumors, its metabolite, (ADO), driver immunosuppression mediated A2A receptors (A2AR) A2B (A2BR) found on tumor-associated lymphoid myeloid cells. This review will focus as key checkpoint inhibitor-like immunosuppressive player how reducing production or blocking A2AR A2BR enhances

Language: Английский

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Role of Cytokines and Other Soluble Factors in Tumor Development: Rationale for New Therapeutic Strategies

Cells, Journal Year: 2023, Volume and Issue: 12(21), P. 2532 - 2532

Published: Oct. 27, 2023

Many cytokines control tumor development by directly lowering cancer cell proliferation and inducing apoptotic death, or indirectly activating the antitumoral activity of specific immune cells such as NK CD8+ T-lymphocytes [...]

Language: Английский

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Plasticity and resistance of cancer stem cells as a challenge for innovative anticancer therapies - do we know enough to overcome this?

PubMed, Journal Year: 2024, Volume and Issue: 23, P. 335 - 355

Published: Jan. 1, 2024

According to the CSC hypothesis, cancer stem cells are pivotal in initiating, developing, and causing recurrence. Since identification of CSCs leukemia, breast cancer, glioblastoma, colorectal 1990s, researchers have actively investigated origin biology CSCs. However, hypothesis role these tumor development model is still debate. These exhibit distinct surface markers, capable self-renewal, demonstrate unrestricted proliferation, display metabolic adaptation. phenotypic plasticity capacity EMT strictly connected stemness state. show high resistance chemotherapy, radiotherapy, immunotherapy. The significantly influenced by microenvironment factors, such as hypoxia. Targeting genetic epigenetic changes cells, together with interactions microenvironment, presents promising avenues for therapeutic strategies. See also Graphical abstract(Fig. 1).

Language: Английский

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CAR T cells secreting NGF-neutralizing scFv enhance efficacy in clear cell renal cell carcinoma by relieving immunosuppression through immunosympathectomy

Journal for ImmunoTherapy of Cancer, Journal Year: 2024, Volume and Issue: 12(12), P. e009910 - e009910

Published: Dec. 1, 2024

Background Chimeric antigen receptor (CAR) T cells have demonstrated remarkable breakthroughs in treating hematologic malignancies, yet their efficacy solid tumors is limited by the immunosuppressive microenvironment. Sympathetic nerves significantly contribute to this milieu tumors. However, impact of tumor sympathetic denervation on enhancing CAR T-cell antitumor remains unclear. Methods We screened for gene sets various types cancers and investigated association with immunosuppression renal clear cell carcinoma. Using antibodies block nerve growth factor (NGF) pathway, we explored distribution tissues progression. Additionally, engineered secrete NGF single chain fragment variable (scFv) achieve immunosympathectomy assessed efficacy. Bulk RNA sequencing single-cell analyses were conducted evaluate changes immune phenotypes within Results Blocking pathway effectively reduced delayed scFv achieved a similar exhibited enhanced suppression. revealed that augmented effect was primarily due inhibition terminal exhaustion phenotype tumor-infiltrating CD8 prevention macrophage polarization from M1 M2. This approach maintained stronger state at site. splenic also more potent effector following infusion scFv-secreting cells. Conclusions Our results suggest novel weaken microenvironment synergistically enhance against

Language: Английский

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