Interleukin-2: Evaluation of Routes of Administration and Current Delivery Systems in Cancer Therapy

Shaker, Mohamed A.; Younes, Husam M.

doi:10.1002/jps.21596

Cited by 43 publications

(39 citation statements)

References 167 publications

(213 reference statements)

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“…While improving protein half-life following injection, these modifications also make the protein more sensitive to acidic environments. 13 To determine the effects of prolonged exposure of rhIL-2 to CDHP on structural integrity, rhIL-2 was incubated for 24h or 48h with 30 or 60mM CDHP (with and without NaHCO 3 ) at 37°C under sterile conditions. At the end of this period, culture media samples were flash frozen and rhIL-2 concentration measured by sandwich ELISA.…”

Section: Resultsmentioning

confidence: 99%

“…13,14 Using rhIL-2 therapy, durable cancer remission is reported in a significant number of patients (5–10%). Due to widespread distribution of the cancer at late disease stages and high clearance rate of rhIL-2, bolus intravenous injections of rhIL-2 are employed to maintain a circulating therapeutic concentration.…”

Section: Introductionmentioning

confidence: 99%

“…The use of high dose-bolus regimes is limited however, due to adverse, often severe, side effects that include malaise, hypotension, hyperthermia, vomiting, diarrhea, edema, and in severe cases, capillary leakage syndrome. 13–15 In vivo studies report that continuous, local rhIL-2 delivery to the tumor site is more efficacious, and is associated with lower toxicity. Several drug delivery systems aimed at delivering a sustained, lower dose of rhIL-2 targeted to the tumor site(s), or relevant immune cells, have been investigated as a means of improving clinical outcome while minimizing side effects associated with bolus administration.…”

Section: Introductionmentioning

confidence: 99%

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In Vitro Assessment of Choline Dihydrogen Phosphate (CDHP) as a Vehicle for Recombinant Human Interleukin-2 (rhIL-2)

et al. 2012

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Choline dihydrogen phosphate (CDHP) is an ionic liquid reported to increase thermal stability of model proteins. The current work investigated CDHP effect on structural integrity and biological activity of recombinant human interleukin-2 (rhIL-2), a therapeutic protein used for treating advanced melanoma. In vitro CDHP biocompatibility was also evaluated using primary cell cultures, or B16-F10 cell line, chronically exposed to the ionic liquid. Formulation of rhIL-2 in an aqueous 680mM CDHP pH 7.4 solution resulted in a 12.5°C increase in the Tm of rhIL-2 compared to a basic buffer formulation, and provided conformational rhIL-2 stabilization when the solution was heated to 23.3°C above the Tm. CDHP solutions (≤80mM), exhibited no cytotoxic activity toward primary splenocytes or B16-F10 cells in culture. However, a 10-fold loss in biological activity was observed when rhIL-2 was used in a 30mM CDHP aqueous solution with NaHCO3 (pH≥7.2) compared to controls without CDHP. While increased Tm is associated with a diminished rhIL-2 biological activity, the therapeutic protein remains structurally intact and functional.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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In Vitro Assessment of Choline Dihydrogen Phosphate (CDHP) as a Vehicle for Recombinant Human Interleukin-2 (rhIL-2)

et al. 2012

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“…Also, the use of organic solvents during the device preparation, which may change the protein conformational structure (denaturation), as reported previously [147].…”

Section: Bioelastomersmentioning

confidence: 89%

“…In such manner, the delivery of highly potent, but relatively toxic, anticancer drugs without inducing tremendous side effect was revealed [98,100,150,151]. These also include DNA delivery [73,125], controlled release of peptide and protein [147,152], and live vaccine delivery [122].…”

Section: Hydrogelsmentioning

confidence: 98%

Photo-irradiation paradigm: Mapping a remarkable facile technique used for advanced drug, gene and cell delivery

Shaker

Younes

2015

Journal of Controlled Release

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Systems Biology and Genomics

Hassan

Heiser

Gray

2017

Holland‐Frei Cancer Medicine

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Overview Cancers are complex, adaptive systems comprised of cancer cells, the proximal and distal cells, and soluble and insoluble proteins that influence the behavior of the cancer cells. Features pertaining to the cancer are referred to as intrinsic to the cancer and those comprising the proximal and distal microenvironments are referred to as extrinsic to the cancer. Genomics studies seek to develop comprehensive cellular and molecular profiles of cancers and cancer systems biology studies seek to develop the experimental and theoretical methods needed to understand how the components work together to determine cancer function. The overall goal of these efforts is to develop the ability to predict the behavior of cancers—including progression and response to therapy—from measurements of the intrinsic and extrinsic molecular and cellular components of the cancers. Here, we review recent progress in international efforts to measure the genomic, epigenomic, and proteomic features (aka omic features) of major tumor types. We summarize work on establishing associations between omic features and cancer behavior. Finally, we summarize the computational and experimental models that are currently being used to understand and manipulate the behavior of complex cancer systems.

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Interleukin-2: Evaluation of Routes of Administration and Current Delivery Systems in Cancer Therapy

Cited by 43 publications

References 167 publications

In Vitro Assessment of Choline Dihydrogen Phosphate (CDHP) as a Vehicle for Recombinant Human Interleukin-2 (rhIL-2)

In Vitro Assessment of Choline Dihydrogen Phosphate (CDHP) as a Vehicle for Recombinant Human Interleukin-2 (rhIL-2)

Photo-irradiation paradigm: Mapping a remarkable facile technique used for advanced drug, gene and cell delivery

Systems Biology and Genomics

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