Effective cancer therapy with a single injection of interleukin-2 at the site of the tumour

Wd, Otter; Cadée, Jenny A.; Gavhumende, R; Cj, De Groot; We, Hennink; Stewart, Rachel

doi:10.1007/s002620050595

Cited by 20 publications

(22 citation statements)

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“…[15,22] It is easy to prospect that the elimination of IL-2 from the tumor would be very fast. So, using this liposomal IL-2 is expected to improve the therapeutic effects or decrease the number of injections, because liposomal IL-2 can enhance the duration time in the dosing area.…”

Section: Resultsmentioning

confidence: 99%

“…[16][17][18] The efficacy of its direct injection into tumor (melanoma) has also been reported. [15] In this study, liposomal IL-2 was administered subcutaneously to mice, and the release of IL-2 into the systemic circulation and its elimination from the dosing area were investigated. Interleukin-2 was released to the systemic circulation from under the skin, continuously.…”

Section: Introductionmentioning

confidence: 99%

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Continuous Release of Interleukin-2 from Liposomal IL-2 (Mixture of Interleukin-2 and Liposomes) After Subcutaneous Administration to Mice

Kanaoka

Takahashi

Yoshikawa

et al. 2003

Drug Development and Industrial Pharmacy

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Recombinant interleukin-2 (IL-2) was strongly and almost completely adsorbed onto small and hydrophobic liposomes by simple mixing under optimal conditions (liposome: DSPC-DSPG; molar ratio, 10:1; 30-50 nm in size, ratio of IL-2 to liposome: 4.0 JRU/nmol lipid). This liposomal IL-2 displayed better distribution after intravenous administration in mice and improved therapeutic effect against experimental M5076 metastases, as reported previously. In this study, the elimination of IL-2 from the dosing area was investigated when the liposomal IL-2 was administered to mice subcutaneously. The results suggest that the release of IL-2 from this liposome was continuous and almost complete. The mean residence time (MRT) of IL-2 in the dosing area was 11.0 +/- 1.65 hr. This resulted in the 8-fold times enhancement of MRT in the systemic circulation by the presence of liposomes, and IL-2 was detected in the serum for 2 days. Using this liposomal IL-2 is expected to have the potential to decrease the number of injections and enhance the efficacy of IL-2 in immunotherapies and therapies against tumor.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Continuous Release of Interleukin-2 from Liposomal IL-2 (Mixture of Interleukin-2 and Liposomes) After Subcutaneous Administration to Mice

Kanaoka

Takahashi

Yoshikawa

et al. 2003

Drug Development and Industrial Pharmacy

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“…The placebo contained distilled water with polygeline. Directly after surgical removal of the tumour, rhIL2 (1 ml containing 4.5 million IU) or placebo was injected evenly into the wound bed (0.01–0.05 ml per site) in an at random double-blinded fashion [20,34]. The wound bed was larger than the tumour by 5 mm in all dimensions and depended on the tension in that specific area.…”

Section: Methodsmentioning

confidence: 99%

“…The treatment was well tolerated and had antitumour activity. Other tumours successfully treated with intratumoural rhIL2 therapy include canine transmissible venereal tumours [34], bovine ocular squamous cell carcinomas [35], equine sarcoid tumours [36], and canine mast cell tumours [37]. …”

Section: Introductionmentioning

confidence: 99%

The effect of interleukin-2 on canine peripheral nerve sheath tumours after marginal surgical excision: a double-blind randomized study

Haagsman

Witkamp

Sjollema³

et al. 2013

BMC Vet Res

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BackgroundThe objective of this study was to evaluate the effect on outcomes of intraoperative recombinant human interleukin-2 injection after surgical resection of peripheral nerve sheath tumours. In this double-blind trial, 40 patients due to undergo surgical excision (<5 mm margins) of presumed peripheral nerve sheath tumours were randomized to receive intraoperative injection of interleukin-2 or placebo into the wound bed.ResultsThere were no significant differences in any variable investigated or in median survival between the two groups. The median recurrence free interval was 874 days (range 48–2141 days), The recurrence-free interval and overall survival time were significantly longer in dogs that undergone the primary surgery by a specialist-certified surgeon compared to a referring veterinarian regardless of whether additional adjunct therapy was given.ConclusionOverall, marginal excision of peripheral nerve sheath tumours in dogs resulted in a long survival time, but adjuvant treatment with recombinant human interleukin-2 (rhIL-2) did not provide a survival advantage.

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“…In this work, we elucidate the molecular diffusion characteristics of 4% mTG‐gels by examining the molecular flux and diffusion coefficient of a model therapeutic protein, human interleukin‐2 (hIL2). hIL2 has been shown to be an effective anticancer therapeutic in various human clinical trials 20–24. Sustained release of this cytokine may be possible with cells engineered to secrete hIL2 and encapsulated in mTG‐gels for implantation.…”

Section: Introductionmentioning

confidence: 99%

Diffusion of interleukin‐2 from cells overlaid with cytocompatible enzyme‐crosslinked gelatin hydrogels

Yung

Bentley

Barbari

2010

J Biomedical Materials Res

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In designing an implantable cell encapsulation construct to continuously deliver therapeutic proteins to a patient, it is critical that the biomaterial be compatible with the encapsulated cells, as well as conducive to the diffusion of desired molecules. As a continuation of our previous work, which demonstrated the cytocompatibility of gelatin hydrogels enzymatically crosslinked by microbial transglutaminase (mTG-gels), this work seeks to elucidate the diffusion properties that are needed for sustained release of therapeutic proteins produced by the engineered cells. HEK293 cells genetically engineered to secrete an anticancer drug, interleukin-2 (hIL2), through 4% mTG-gels used as a 1D diffusion model. Under steady-state conditions, cells secrete hIL2 at a therapeutic rate of 5.0-5.7 ng/cm(2)/h/10(6) cells. The diffusion coefficient of hIL2 through the hydrogels is D(m) = 4.0 x 10(-7) cm(2)/s. This value is comparable with similarly sized proteins through hydrogels and is further verified by modeling nonsteady-state diffusion through various thicknesses of the hydrogels, as well as by acellular diffusion chamber experiments. These findings demonstrate that the enzymatically crosslinked hydrogels are not only cytocompatible but also have suitable transport properties that will facilitate the design of sustained drug release devices.

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Effective cancer therapy with a single injection of interleukin-2 at the site of the tumour

Cited by 20 publications

References 0 publications

Continuous Release of Interleukin-2 from Liposomal IL-2 (Mixture of Interleukin-2 and Liposomes) After Subcutaneous Administration to Mice

Continuous Release of Interleukin-2 from Liposomal IL-2 (Mixture of Interleukin-2 and Liposomes) After Subcutaneous Administration to Mice

The effect of interleukin-2 on canine peripheral nerve sheath tumours after marginal surgical excision: a double-blind randomized study

Diffusion of interleukin‐2 from cells overlaid with cytocompatible enzyme‐crosslinked gelatin hydrogels

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