Potential targeting of the tumor microenvironment to improve cancer virotherapy

Liao, Zi-Xian; Hsu, Shan-hui; Tang, Shiue-Cheng; Kempson, Ivan; Yang, Pan-Chyr; Tseng, S. Ja

doi:10.1016/j.pharmthera.2023.108521

Cited by 6 publications

(4 citation statements)

References 128 publications

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“…Remarkable accomplishments in preclinical and clinical utilization of AAV have firmly established AAV as effective therapeutic vectors [ 10 , 11 ]. This recognition is further emphasized by the regulatory approval of two AAV-based therapies in Europe and the United States [ 10 , 12 , 13 ]. In principle AAV2 promote dose escalation for systemic delivery, however the majority of the vector still ultimately accumulates in the liver [ 15 ] and current formulations lack control over in situ release and subsequent infection of target cells for effective virotherapy [ 10 , 13 ].…”

Section: Discussionmentioning

confidence: 99%

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Nano-modified viruses prime the tumor microenvironment and promote the photodynamic virotherapy in liver cancer

Ou,

Liao,

Kempson

et al. 2024

J Biomed Sci

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Background As of 2020, hepatocellular carcinoma (HCC), a form of liver cancer, stood as the third most prominent contributor to global cancer-related mortality. Combining immune checkpoint inhibitors (ICI) with other therapies has shown promising results for treating unresectable HCC, offering new opportunities. Recombinant adeno-associated viral type 2 (AAV2) virotherapy has been approved for clinical use but it efficacy is stifled through systemic administration. On the other hand, iron oxide nanoparticles (ION) can be cleared via the liver and enhance macrophage polarization, promoting infiltration of CD8+ T cells and creating a more favorable tumor microenvironment for immunotherapy. Methods To enhance the efficacy of virotherapy and promote macrophage polarization towards the M1-type in the liver, ION-AAV2 were prepared through the coupling of ION-carboxyl and AAV2-amine using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC)/N-hydroxysulfosuccinimide (Sulfo-NHS). Efficacy after systemic delivery of ION-AAV2 in an orthotopic HCC model was evaluated. Results After 28 days, the tumor weight in mice treated with ION-AAV2 was significantly reduced by 0.56-fold compared to the control group. The ION-AAV2 treatment led to an approximate 1.80-fold increase in the level of tumor associated M1-type macrophages, while the number of M2-type macrophages was reduced by 0.88-fold. Moreover, a proinflammatory response increased the population of tumor-infiltrating CD8+ T cells in the ION-AAV2 group. This transformation converted cold tumors into hot tumors. Conclusions Our findings suggest that the conjugation of ION with AAV2 could be utilized in virotherapy while simultaneously exploiting macrophage-modulating cancer immunotherapies to effectively suppress HCC growth.

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Section: Discussionmentioning

confidence: 99%

“…AAV2 has been used in over 40% of clinical trials, particularly for liver-specific targeting [ 11 ]. Since 2017, three gene therapies utilizing recombinant AAV have gained approval [ 10 , 12 , 13 ]. However, the systemic administration of these therapies still presents significant challenges [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Nano-modified viruses prime the tumor microenvironment and promote the photodynamic virotherapy in liver cancer

Ou,

Liao,

Kempson

et al. 2024

J Biomed Sci

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“…The ECM is a key constitutive part of the TME, consisting principally of reactive tissue components including glycoproteins, collagens, and many enzymes that have an impact on cell adhesion, proliferation, and communication. These substances can change their physical properties, composition, and the environment in which they live to affect tumor cell migration, while the concentration of ECM also determines the ratio of tumor cell migration from one region to another (72)(73)(74)(75)(76). Additionally, nonmalignant cells in the TME are prominently separated into two primary groups, immune cells and mesenchymal stromal cells, which stimulate and promote uncontrolled cell proliferation to affect all stages of carcinogenesis (77)(78)(79).…”

Section: The Overview Of Tamsmentioning

confidence: 99%

Exosome-mediated communication between gastric cancer cells and macrophages: implications for tumor microenvironment

Qiu,

Lu,

et al. 2024

Front. Immunol.

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Gastric cancer (GC) is a malignant neoplasm originating from the epithelial cells of the gastric mucosa. The pathogenesis of GC is intricately linked to the tumor microenvironment within which the cancer cells reside. Tumor-associated macrophages (TAMs) primarily differentiate from peripheral blood monocytes and can be broadly categorized into M1 and M2 subtypes. M2-type TAMs have been shown to promote tumor growth, tissue remodeling, and angiogenesis. Furthermore, they can actively suppress acquired immunity, leading to a poorer prognosis and reduced tolerance to chemotherapy. Exosomes, which contain a myriad of biologically active molecules including lipids, proteins, mRNA, and noncoding RNAs, have emerged as key mediators of communication between tumor cells and TAMs. The exchange of these molecules via exosomes can markedly influence the tumor microenvironment and consequently impact tumor progression. Recent studies have elucidated a correlation between TAMs and various clinicopathological parameters of GC, such as tumor size, differentiation, infiltration depth, lymph node metastasis, and TNM staging, highlighting the pivotal role of TAMs in GC development and metastasis. In this review, we aim to comprehensively examine the bidirectional communication between GC cells and TAMs, the implications of alterations in the tumor microenvironment on immune escape, invasion, and metastasis in GC, targeted therapeutic approaches for GC, and the efficacy of potential GC drug resistance strategies.

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“…In 2017, recombinant adenovirus (AAV) drug delivery for cancer treatment was approved for clinical application, which proved the feasibility of its viral drug delivery and has become a potential treatment for cancer treatment. However, the cases of virus application in the field of thrombus diagnosis and treatment are relatively rare [129,130]. In order to effectively fight and treat thrombosis, it is particularly important to develop a method that can accurately locate the location of thrombus lesions and monitor the thrombolysis.…”

Section: Biologically Inspired Delivery Of Biomimetic Nanoparticlesmentioning

confidence: 99%

Advances in Nano-Functional Materials in Targeted Thrombolytic Drug Delivery

Ren,

Mi,

Wei

et al. 2024

Molecules

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Thrombotic disease has been listed as the third most fatal vascular disease in the world. After decades of development, clinical thrombolytic drugs still cannot avoid the occurrence of adverse reactions such as bleeding. A number of studies have shown that the application of various nano-functional materials in thrombus-targeted drug delivery, combined with external stimuli, such as magnetic, near-infrared light, ultrasound, etc., enrich the drugs in the thrombus site and use the properties of nano-functional materials for collaborative thrombolysis, which can effectively reduce adverse reactions such as bleeding and improve thrombolysis efficiency. In this paper, the research progress of organic nanomaterials, inorganic nanomaterials, and biomimetic nanomaterials for drug delivery is briefly reviewed.

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Potential targeting of the tumor microenvironment to improve cancer virotherapy

Cited by 6 publications

References 128 publications

Nano-modified viruses prime the tumor microenvironment and promote the photodynamic virotherapy in liver cancer

Nano-modified viruses prime the tumor microenvironment and promote the photodynamic virotherapy in liver cancer

Exosome-mediated communication between gastric cancer cells and macrophages: implications for tumor microenvironment

Advances in Nano-Functional Materials in Targeted Thrombolytic Drug Delivery

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