Method for administering TRAIL-like protein to continuously inhibit tumor cell growth

A technology for tumor cells and drug delivery methods, which is applied in the field of drug delivery where TRAIL-like proteins continue to inhibit the growth of tumor cells, and can solve problems such as insufficient experimental basis, unexplored intravenous injection, interval, repeated efficacy, and different treatment responses.

Inactive Publication Date: 2018-12-21
CHENGDU HUACHUANG BIOTECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The above experimental results show that once a day (1 hour / day), continuous intravenous injection for 5 days does not inhibit tumor growth continuously (in a treatment cycle of 21 days), and this dosage regimen is not Apo2L / Optimal dosing regimen for TRAIL
[0015] The dosing regimen determined by Genentech Inc has at least four deficiencies: (1) Tumor cells with different sensitivities have different therapeutic responses to Apo2L / TRAIL, and the data source for the Apo2L / TRAIL dosing regimen is mainly based on its sensitivity to highly sensitive and The inhibitory effect on moderately sensitive tumor cells does not fully represent its actual effect on relatively drug-resistant tumor cells, so the experimental basis for determining the dosage regimen is not comprehensive enough and the applicability is limited
(2) Even for highly sensitive and moderately sensitive tumor cells, the intravenous injection of Apo2L / TRAIL once a day for 5 consecutive days still cannot sustain the growth of tumor cells
(3) Genentech Inc did not explore the difference in the efficacy of prolonged administration of Apo2L / TRAIL (intravenous injection, once a day, for 10 consecutive days or 15 days) and intravenous injection, once a day, for 5 consecutive days
(4) Genentech Inc did not explore the difference in the efficacy of Apo2L / TRAIL intravenous injection, interval, repeated, multiple administration and intravenous injection, once a day, 5 consecutive days of administration

Method used

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  • Method for administering TRAIL-like protein to continuously inhibit tumor cell growth
  • Method for administering TRAIL-like protein to continuously inhibit tumor cell growth
  • Method for administering TRAIL-like protein to continuously inhibit tumor cell growth

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0095] Study on time-effect relationship of TRAIL-Mu3 and TRAIL-MuR5S4TR inhibiting tumor cell growth in vitro

[0096] 1. Research purpose

[0097] To study the tumor inhibitory effect of different concentrations (doses) of TRAIL-Mu3 and TRAIL-MuR5S4TR on human lung cancer cells NCI-H460, Calu-1, NCI-H1299 in vitro and its relationship with time.

[0098] 2. Experimental materials, reagents and equipment

[0099] 2.1 Preliminary experiment

[0100] 2.1.1 Cell selection: Based on the previous experimental data, (see Table 1) three strains of cells with different degrees of sensitivity were selected for the formal experiment.

[0101] Table 1. In vitro tumor inhibitory effects of TRAIL-Mu3 and TRAIL-MuR5S4TR on seven lung cancer cell lines

[0102]

[0103]

[0104] Based on the data in the above table, considering the effects of TRAIL-Mu3 and TRAIL-MuR5S4TR, a sensitive strain: NCI-H460; an insensitive strain: NCI-H1299; and a moderately sensitive strain: calu-1 were ...

Embodiment 2

[0145] Study on anti-tumor effect of different administration times of TRAIL on human lung cancer NCI-H460 cell xenograft tumor in nude mice

[0146] 1. Purpose of the experiment

[0147] Intravenous injection of 60 mg / kg once a day for 5 consecutive days (Schedule 1: 5 times in total), intravenous injection of 60 mg / kg once a day for 5 consecutive days and then continuous injection for 5 days at intervals of 2 days (Scheme 2: a total of 10 times) or 60mg / kg dose of intravenous injection, once a day, continuous injection for 5 days after an interval of 2 days, and another continuous injection for 5 days after an interval of 2 days again (Scheme 3: a total of 15 times) ) three different administration regimens, and compare the differences in the anti-tumor activity in the human lung cancer NCI-H460 nude mouse xenograft model in vivo at three different administration times.

[0148] 2. Experimental animals

[0149] 2.1 Animal species

[0150] mice.

[0151] 2.2 Varieties

...

Embodiment 3

[0233] Study on the therapeutic effect of TRAIL-Mu3 and TRAIL-MuR5S4TR at different dosing intervals on human lung cancer NCI-H460 xenograft tumor in nude mice

[0234] 1. Purpose of the experiment

[0235] In this study, the human lung cancer NCI-H460 nude mouse xenograft tumor model was used to evaluate the difference in the in vivo anti-tumor activity of TRAIL-Mu3 and TRAIL-MuR5S4TR at different dosing intervals.

[0236] 2. Experimental animals

[0237] 2.1 Animal species

[0238] mice.

[0239] 2.2 Varieties

[0240] Balb / c nude mice.

[0241] 2.3 Gender

[0242] female.

[0243] 2.4 Quantity

[0244] 90 rats were inoculated, and 64 rats were selected.

[0245] 2.5. Age

[0246] 4-6 weeks.

[0247] 2.6. Weight

[0248] 16 ~ 18g ± 20% weight mean.

[0249] 2.7. Animal origin (supplier)

[0250]Shanghai Xipuer-Bikay Laboratory Animal Co., Ltd. (BK), license number SCXK (Shanghai) 2013-0016, animal certificate number: 2008001661519.

[0251] 2.8. Experimental a...

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Abstract

The invention provides a method for administering TRAIL-like protein to continuously inhibit tumor cell growth, which is a method for intermittent, repeated and full-course drug exposure. By increasing the interval of administration, increasing the exposure time of tumor cells in the whole course of treatment, the effect of the drug in the entire course of treatment is not attenuated, thereby continuing to inhibit tumor growth.

Description

technical field [0001] The invention relates to the field of medicine, in particular to a drug administration method for TRAIL proteins to continuously inhibit the growth of tumor cells. Background technique [0002] TRAIL is a member of the tumor necrosis factor (Tumor necrosis factor, TNF) superfamily, and its gene sequence was independently cloned by Wiley et al. in 1995 and Pitti et al. in 1996. body (Apo2ligand, Apo2L). Subsequent studies confirmed that Apo2L and TRAIL are essentially the same protein, so it can be customarily called Apo2L / TRAIL. The function of TRAIL is firstly as a regulator of the organism's innate or acquired immunity, and secondly, it plays an anti-tumor role as an immune surveillance in the exogenous cell apoptosis pathway. The biggest advantage of TRAIL is that it can selectively induce the apoptosis of various tumor cells without any toxicity to normal cells. Research data show that, whether in vitro or in vivo, Apo2L / TRAIL is effective for h...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/17A61P35/00A61P35/02
CPCA61K38/177A61P35/00A61P35/02A61K38/17A61K39/395C07K16/28
Inventor 陈守春闫娟徐琦胡海洋黄先洲魏利佳
Owner CHENGDU HUACHUANG BIOTECH CO LTD
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