This patent application has not been assigned to a company or institution.
The following quote was obtained by the news editors from the background information supplied by the inventors: "Complete surgical resection and combined chemoradiation represent the hallmarks for curative treatment of many cancer cancer patients. However, complete resection cannot always be achieved, especially for large tumors and tumors close to anatomical structures which cannot be removed (e.g. large vessels, nerves, and central nervous system). In addition, loco-regional recurrence remains a significant problem and adversely affects overall survival.
"To eradicate residual tumor cells local radiation or combined chemoradiation therapy is recommended to be initiated within 8 weeks of surgery. However, patient compliance is limited with about a quarter of the patients choosing to omit or delay post-operative chemo-radiation. In addition, clinical, psychological or social factors can lead to prolonged delays in chemoradiation treatment initiation ranging from 3 months to 1 year after surgery.
"Omission or significant delay of postsurgical radiotherapy and/or chemotherapy significantly reduces overall survival. Accordingly, it is desired to advance the art with new, safe, effective and easy-to-apply treatment options that can bridge the gap between surgery and adjuvant chemo-radiation to suppress tumor growth in the interim time period and ultimately, improve patient survival. The present invention bridges this gap."
In addition to the background information obtained for this patent application, NewsRx journalists also obtained the inventor's summary information for this patent application: "An immuno-therapy for treatment of a tumor is provided. An effective dose of a pharmaceutically accepted composition is administered in vivo to cancer cells of a tumor. The composition contains superparamagnetic iron oxide nanoparticles. Examples of useful nanoparticles are ferumoxytol, ferumoxtran-10 or ferumoxides. In one variation, the compositions could be chemically modified to attract or activate immune cells (such as macrophages or T-cells).
"The effective dose is defined as: (i) 1-50 mg Fe/kg body weight and/or (ii) 1-10 mg Fe/ml of an administered iron product concentration. These doses, as described herein, are considered low doses and they do not cause (direct) cytotoxic effects to the cancer or normal/healthy cells.
"Once the composition has been administered and during the immuno-therapy period, it is recommended to avoid any means that would cause direct cytotoxic effects to the cancer cells and to normal/healthy tissue. Examples on how such cytotoxic effects could be achieved are, for example, but not limited to: (i) heat applied to the composition-administered cancer cells, (ii) irradiation energy applied to the composition-administered cancer cells, (iii) a release of a toxic agent by the administered composition or to the administered composition, or (iv) any combination of these examples.
"The combination of composition-administered cancer cells with the avoidance of direct cytotoxic effects during the period of the immuno-therapy has been shown to be successful to inhibit the growth of the cancer cells or to result in aptosis of the cancer cells.
"Progress of the immuno-therapy can be evaluated using Magnetic Resonance Imaging (MRI, while the therapy is ongoing) to image: (i) the tumor to determine a size of the tumor, and/or (ii) the composition-administered to the cancer cells to determine the amount of the composition remaining in an enviroment of the cancer cells. It is noted that MRI used for these purposes does not cause direct cytotoxic effects to the cancer cells and to normal/healthy tissue. The imaging steps could be performed in a single imaging procedure or different imaging procedures. The determination of (i) and (ii) can be performed semi- or fully automatic by computer software either in conjunction with an MR imaging system or as part of an MR imaging system.
"When it is determined that: (i) the tumor starts to grow and/or (ii) the remaining composition falls below a threshold, then an additional effective dose of the pharmaceutically accepted composition can be administered in vivo to the cancer cells of the tumor or the remaining cancer cells of the tumor. These additional doses falls in the same ranges as described supra.
"The immuno-therapy of this invention is a safe (due to the lack of any concomitant local or systemic toxic side effects), clinically applicable, ready-to-use theranostic approach for cancer patients who are unable to start chemoradiotherapy in a timely manner, i.e. an effective interim or adjunctive treatment for patients. The immuno-therapy bridges the gap between surgery and adjuvant chemo-radiation to suppress tumor growth in the interim time period and ultimately, improve patient survival.
BRIEF DESCRIPTION OF THE DRAWINGS
"The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
"FIG. 1 shows the immuno-therapy for tumor treatment method according to an exemplary embodiment of the invention.
"FIG. 2 shows according to an exemplary embodiment of the invention iron oxide nanoparticles inhibition of tumor growth. Shown is a photo of a mouse at 16 days after co-implantation of 1.3 million PyMT-MMTV cancer cells with ferumoxytol (USPIO) or cancer cells only (control).
"FIG. 3 shows an intra-individual comparison according to an exemplary embodiment of the invention. Decreased tumor volume of ferumoxytol-treated and untreated tumors at different time points after tumor inocculation. Data are displayed as means and standard deviations of n=10 tumors for the 10 mg Fe/kg dose group and controls (cancer-UL) as well as n=7 tumors for the 29.7 mg Fe/kg dose group and controls (cancer).
"FIG. 4 shows an inter-individual comparison according to an exemplary embodiment of the invention. Decreased tumor volume of ferumoxtran-10-treated and untreated tumors at different time points after tumor inocculation. Data are displayed as means and standard deviations of n=6 tumors and controls.
"FIG. 5 is an example indicating that ultrasmall paramagnetic iron oxide nanoparticles (USPIO) metabolization disinhibits tumor growth. FIG. 5 shows according to an exemplary embodiment of the invention in vivo MR imaging of iron oxide nanoparticles. Axial T2-weighted MR images of representative MMTV-PyMT mammary tumors at different time points after co-implantation of cancer cells and ferumoxytol (white arrow) and cancer cells only (red arrow). The iron oxide nanoparticle-based contrast agents cause a negative (dark) signal effect on these scans (white arrow).
"FIG. 6 is another example indicating that ultra-small paramagnetic iron oxide nanoparticles (USPIO) metabolization disinhibits tumor growth. FIG. 6 shows according to an exemplary embodiment of the invention quantitation of iron-induced MR signal (T2*relaxation rates) of coimplantation sites and muscle as internal control up to 21 days after inoculation. Data are displayed as means of 10 implantation sites and standard deviations. *indicates significant difference (p
"FIG. 7 shows according to an exemplary embodiment of the invention that low dose (low as defined herein) ferumoxytol does not induce cytotoxic effects on cancer cells. Relative caspase 3/7 activities, assessed by AMC Caspase-3/7 assay, demonstrate no significant toxic effect on a variety of cell lines up to an exposure with 8.37 mg Fe/ml ferumoxytol. Further increase in ferumoxytol concentrations induced a mild, dose-dependent cytotoxic effect. Data were collected from 3 independent experiments per cell line.
"FIG. 8 shows according to an exemplary embodiment of the invention USPIO increased macrophage migration. Macrophage-cancer cell co-culture set up in transwell chambers. DiD-labeled macrophages were seeded onto the insert and cancer cells were seeded onto the bottom chamber. Ferumoxytol was added to the lower chamber. Macrophage migration was analyzed 6 hours after addition of ferumoxytol at 2.73 mg/ml (equivalent to 10 mg Fe/kg used in in vivo studies calculated from the average animal weight) or
"FIG. 9 shows according to an exemplary embodiment of the invention corresponding macrophage counts in the lower chamber, averaged from counts in 15-20 fields at 10.times.
"FIG. 10 shows according to an exemplary embodiment of the invention representative fluorescence images at 10.times. magnification demonstrate migration of more DiD-positive (red) macrophages towards lower chambers with cancer cells and ferumoxytol than chambers with cancer cells or ferumoxytol alone. Cell nuclei are counterstained with DAPI.
"FIG. 11 shows according to an exemplary embodiment of the invention USPIO induced macrophage-mediated cancer cell apoptosis. Representative F-actin/rhodamine (red) and DAPI stains (upper row) as well as Caspase-3 immunostains (green, lower row) of cells in transwell coculture system (red). Cancer cells, incubated with both macrophages and ferumoxytol induce higher number of apoptotic cells than cancer cells incubated with macrophages or ferumoxytol alone.
"FIG. 12 shows according to an exemplary embodiment of the invention USPIO upregulated M1-associated gene expression and downregulated M2-associated gene expression. Gene expression profiles of macrophages, incubated with cancer cells, ferumoxytol or both, measured by qRT-PCR. Data were collected from 3 independent experiments with triplicates each."
URL and more information on this patent application, see: Daldrup-Link, Heike E. Immuno-Therapy for Cancer Treatment Using Iron Oxide Nanoparticles. Filed
Keywords for this news article include: Patents, Therapy, Caspases, Treatment, Phagocytes, Macrophages, Nanoparticle, Myeloid Cells, Nanotechnology, Peptide Hydrolases, Emerging Technologies, Enzymes and Coenzymes, Cysteine Endopeptidases.
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