2022
DOI: 10.3389/fonc.2022.1017612
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Clinically relevant dosing and pharmacokinetics of DNA-encoded antibody therapeutics in a sheep model

Abstract: DNA-encoded delivery and in vivo expression of antibody therapeutics presents an innovative alternative to conventional protein production and administration, including for cancer treatment. To support clinical translation, we evaluated this approach in 18 40-45 kg sheep, using a clinical-matched intramuscular electroporation (IM EP) and hyaluronidase-plasmid DNA (pDNA) coformulation setup. Two cohorts of eight sheep received either 1 or 4 mg pDNA encoding an ovine anti-cancer embryonic antigen (CEA) monoclona… Show more

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Cited by 5 publications
(9 citation statements)
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“…In our investigations encompassing both murine and rabbit models, we explored the timing of muscle pretreatment with hyaluronidase. While pDNA coformulated with hyaluronidase has been previously used in gene electrotransfer applications [ 46 , 47 , 48 ], its efficacy compared to hyaluronidase pretreatment has not been investigated. Notably, we observed no significant differences in protein production levels when pretreating the muscle with hyaluronidase either 30 min or 5 min prior to plasmid injection and electroporation.…”
Section: Discussionmentioning
confidence: 99%
“…In our investigations encompassing both murine and rabbit models, we explored the timing of muscle pretreatment with hyaluronidase. While pDNA coformulated with hyaluronidase has been previously used in gene electrotransfer applications [ 46 , 47 , 48 ], its efficacy compared to hyaluronidase pretreatment has not been investigated. Notably, we observed no significant differences in protein production levels when pretreating the muscle with hyaluronidase either 30 min or 5 min prior to plasmid injection and electroporation.…”
Section: Discussionmentioning
confidence: 99%
“…Sample collection was performed at multiple timepoints post treatment (1,4,7,14,21,42, and 84 days). At each timepoint, muscle isolation was performed for 5 mice.…”
Section: Sample Collectionmentioning
confidence: 99%
“…This is comparable to the levels observed in sheep, where peak plasma levels reached 5 µg/mL after administration of 12 mg pOVAC in the absence of anti-drug antibodies. Sheep are more similar to humans in terms of body weight, musculature, and blood volume, and therefore these data provide valuable insights towards clinical translation [7]. For a broad implementation of DNA-based mAb delivery, a more stable expression profile at high mAb concentrations would be beneficial.…”
Section: Introductionmentioning
confidence: 99%
See 1 more Smart Citation
“…DMAbs hold promise to accelerate the deployment of new therapeutic interventions and provide preclinical tools for rapid evaluation of biological products. DMAbs have been tested for IgG production targeting prevention and treatment of diverse infectious diseases [15,20,22,23,25,28–36,37 ▪ ,38 ▪▪ ], and cancer [39–45] (Table 1. Current approaches for DNA delivery of antibodies).…”
Section: Introductionmentioning
confidence: 99%