Systemic adenoviral gene delivery to orthotopic murine breast tumors with ablation of coagulation factors, thrombocytes and Kupffer cells

Koski, Anniina; Rajecki, Maria; Guse, Kilian; Kanerva, Anna; Ristimäki, Ari; Pesonen, Sari; Escutenaire, Sophie; Hemminki, Akseli

doi:10.1002/jgm.1373

Cited by 31 publications

(26 citation statements)

References 52 publications

(73 reference statements)

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“…injection, but these two detargeting strategies nevertheless do not significantly decrease viral genomes in the liver or increase viral genomes in the tumor at short time points [120]. In contrast, when Koski et al treated mice with warfarin to deplete vitamin K dependent blood factor interactions, anti-platelet antibodies, and Kupffer cell scavenger receptor blockers into mice prior to Ad injection, the combination of these treatments yielded an 81% increase in tumor to liver ratio of virus [128]. …”

Section: Adenoviral Vector Detargetingmentioning

confidence: 99%

Advances and Future Challenges in Adenoviral Vector Pharmacology and Targeting

Khare

Chen

Weaver³

et al. 2011

CGT

129

138

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Adenovirus is a robust vector for therapeutic applications, but its use is limited by our understanding of its complex in vivo pharmacology. In this review we describe the necessity of identifying its natural, widespread, and multifaceted interactions with the host since this information will be crucial for efficiently redirecting virus into target cells. In the rational design of vectors, the notion of overcoming a sequence of viral “sinks” must be combined with re-targeting to target populations with capsid as well as shielding the vectors from pre-existing or toxic immune responses. It must also be noted that most known adenoviral pharmacology is deduced from the most commonly used serotypes, Ad5 and Ad2. However, these serotypes may not represent all adenoviruses, and may not even represent the most useful vectors for all purposes. Chimeras between Ad serotypes may become useful in engineering vectors that can selectively evade substantial viral traps, such as Kupffer cells, while retaining the robust qualities of Ad5. Similarly, vectorizing other Ad serotypes may become useful in avoiding immunity against Ad5 altogether. Taken together, this research on basic adenovirus biology will be necessary in developing vectors that interact more strategically with the host for the most optimal therapeutic effect.

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Section: Adenoviral Vector Detargetingmentioning

confidence: 99%

Advances and Future Challenges in Adenoviral Vector Pharmacology and Targeting

Khare

Chen

Weaver³

et al. 2011

CGT

129

138

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“…13, 14, 54 Recently, a number of studies demonstrated that adenoviruses can use scavenger receptor A as a direct route to enter Kupffer cells. 15, 49, 55 Administration of poly(I) into mice prior to adenovirus injection significantly reduced the capacity of Kupffer cells to trap adenoviral particles, although the impact of poly(I) pre-dosing on antitumor activity of the adenoviral vector was not evaluated in that study. Here, we confirmed that MV is able to bind to scavenger receptors on macrophage cells and this route of entry was inhibited more than 99% by poly(I) and poly(A) on the murine macrophage J774.1 cell line.…”

Section: Discussionmentioning

confidence: 99%

“…It is important to point out that poly(I) is a single stranded RNA and is less effective at inducing IFN-alpha in leukocytes compared to double stranded small RNA polyI:C. 56 Systemic administration of poly(I) at 0.2 mg per mouse induced no observable toxicity in livers of athymic mice although transient higher serum levels of IL-6, MCP-1 and TNF-α were detected. 55 Alternative ligands of scavenger receptor A could be tested in lieu of poly(I) if clinical testing is desired, for example, fucoidan 46, 57 or using an alternative strategy to transiently eliminate macrophages using clodronate loaded liposomes. 58 While polyI:C has been given as adjuvant in vaccination protocols in human studies 59 and fucoidan has been given orally to humans 60, 61 , intravenous administration of poly(I), fucoidan or clodronate liposomes in humans has not been reported.…”

Section: Discussionmentioning

confidence: 99%

Polyinosinic acid decreases sequestration and improves systemic therapy of measles virus

et al. 2011

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Off target binding or vector sequestration can significantly limit the efficiency of systemic virotherapy. We report here that systemically administered oncolytic measles virus (MV) was rapidly sequestered by the mononuclear phagocytic system (MPS) of the liver and spleen in measles receptor CD46-positive and CD46-negative mice. Since scavenger receptors on Kupffer cells are responsible for the elimination of blood-borne pathogens, we investigated here if MV uptake was mediated by scavenger receptors on Kupffer cells. Pretreatment of cells with poly(I), a scavenger receptor ligand, reduced MV expression by 99% in murine (J774A.1) macrophages and by 50% in human (THP-1) macrophages. Pre-dosing of mice with poly(I) reduced MPS sequestration of MV and increased circulating levels of MV by 4 to 15-folds at 2 minutes post virus administration. Circulating virus was still detectable 30 mins post infusion in mice predosed with poly(I) while no detectable MV was found at 5–10 min post infusion if mice did not receive poly(I). MPS blockade by poly(I) enhanced virus delivery to human ovarian SKOV3ip.1 and myeloma KAS6/1 xenografts in mice. Higher gene expression and improved control of tumor growth was noted early post therapy. Based on these results, incorporation of MPS blockade into MV treatment regimens is warranted.

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“…However, rapid uptake of plasmid DNA could be saturated at high doses of plasmid [64,[142][143][144][145][146]. Polyinosinic acid, a known inhibitor of scavenger receptors, has also been used to inhibit the rapid uptake of viruses and improve their gene transfer efficiency in hepatocytes and tumors [137,140,141,[147][148][149][150][151].…”

Section: Nanoparticle Circulatory Half-life Depends On Evading Liver mentioning

confidence: 99%

“Evolving nanoparticle gene delivery vectors for the liver: What has been learned in 30 years”

Crowley

Rice

2015

Journal of Controlled Release

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Systemic adenoviral gene delivery to orthotopic murine breast tumors with ablation of coagulation factors, thrombocytes and Kupffer cells

Cited by 31 publications

References 52 publications

Advances and Future Challenges in Adenoviral Vector Pharmacology and Targeting

Advances and Future Challenges in Adenoviral Vector Pharmacology and Targeting

Polyinosinic acid decreases sequestration and improves systemic therapy of measles virus

“Evolving nanoparticle gene delivery vectors for the liver: What has been learned in 30 years”

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