Split doses of phospholipid ether analogs for treatment of cancer

A cancer and dose technology, applied in preparations for in vivo experiments, drug combinations, in vivo radioactive preparations, etc., can solve problems such as reducing the therapeutic effect of radiopharmaceuticals

Pending Publication Date: 2022-07-08
SELECTA BIOSCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Uptake of non-target tissues can reduce the effect of radiopharmaceutical therapy by, for example, overexposure of radiosensitive tissues to the administered radiation

Method used

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  • Split doses of phospholipid ether analogs for treatment of cancer
  • Split doses of phospholipid ether analogs for treatment of cancer
  • Split doses of phospholipid ether analogs for treatment of cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0088] The OPM-2 cell line (human multiple myeloma) was purchased from the American Type Culture Collection (ATCC, Rockville, MD) and maintained in McCoy's 5a medium supplemented with 10% fetal bovine serum. Female CB17 SCID mice, approximately 5-7 weeks old, were injected subcutaneously with 1 × 10 7 Viable cells (in -100 [mu]L Dulbecco's PBS). When the tumor size reaches a predetermined size (approximately 150-200 mm 3) to start the study. Potassium iodide concentration 0.1% potassium iodide in drinking water was administered to mice 3 days before injection and for 2 weeks after injection to block free iodide that may be present in the drug formulation. Mice were randomized into multiple dose groups. During the study, tumor volumes were measured using calipers. Tumor doubling time is calculated as TDT = D x log(2) / log(1 + r / 100), where D is the number of days between measurements and r = growth rate; r / 100 = (V2 - V1 / V1) x 100% . Statistical analysis: One-way ANOVA, Du...

Embodiment 2

[0093] Repeated / fractionated doses of CLR131 were well tolerated and better tolerated than a single equivalent dose. All CLR131 doses exhibited significant antitumor activity in this multiple myeloma model. Single-dose infusion yielded similar MM inhibition results to bortezomib. Fractionation of the dose resulted in a statistically significant reduction in tumor volume after 26 days compared to the control group. The split dose resulted in a statistically significant reduction in tumor volume at 52 days (p<0.05) compared to all other treatments. Tumor doubling time was significantly increased with fractionated doses compared to all other treatments. Fractional doses resulted in a statistically significant survival benefit.

Embodiment 3

[0095] As shown in Table 2, the split dose (cohort 5) delivered 18% more drug compared to the single bolus dose (cohort 4), as measured by the actual millicurie dose delivered to the patient. However, the mean magnitude of adverse events decreased and the median magnitude remained unchanged despite giving patients more medication. In addition, efficacy assessments also demonstrated improvement between single bolus doses and split-dose regimens. Median overall survival improved from 6.5 months (single bolus dose) to 7.4 months (fractionated dose), and the assessment of median overall survival in the split-dose group is still ongoing. Mean progression-free survival increased from 2.8 months to 2.9 months, respectively, reassessed in the split-dose group. The mean reduction in surrogate measures of efficacy was greater between cohorts, with a mean reduction of 29% in the cohort of patients who received a single bolus dose and a mean reduction of 40% in the cohort of patients who...

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Abstract

Disclosed herein is a split dose regimen of < 131 > I-labeled 18-(p-iodophenyl) octadecyl phosphorylcholine for use in the treatment of cancer. The dose regimen may include a single dose cycle or a multi-dose cycle. The radiation therapies described herein may be administered according to a first dose cycle and a second dose cycle, as well as the delays necessary in both cycles due to a medical cause of the subject.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS [0002] This application claims the benefit of and priority to US Provisional Patent Application No. 62 / 913,522, filed October 10, 2019, the contents of which are incorporated herein by reference in their entirety. technical field [0003] The present disclosure relates to the use of radiolabeled phospholipid analogs in specific dosage cycles for cancer therapy. Background technique [0004] Selective retention of radiolabeled phospholipid ether analogs in various model systems is limited by problems associated with faster clearance of radiopharmaceuticals and / or accumulation of compounds in non-target tissues. The uptake of non-target tissues can reduce the efficacy of radiopharmaceutical therapy by, for example, over-exposure of radiosensitive tissues to the administered radiation. [0005] There is an urgent need in the art for radiopharmaceuticals with rapid clearance from non-target tissues and a long half-life in plasma...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K51/04
CPCA61K51/0408A61P35/00
Inventor J·隆科尔
Owner SELECTA BIOSCI
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