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Combining adenovirus and chemotherapeutic agents for treating cancer

A chemotherapeutic agent, adenovirus technology, applied in the medical field, can solve problems such as incurable human mesothelioma

Active Publication Date: 2018-09-04
TARGOVAX
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Despite advances in conventional cancer treatment options, human mesothelioma remains incurable and new treatment options are urgently needed

Method used

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  • Combining adenovirus and chemotherapeutic agents for treating cancer
  • Combining adenovirus and chemotherapeutic agents for treating cancer
  • Combining adenovirus and chemotherapeutic agents for treating cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0183] Example 1. The combination of ONCOS-102 and first-line chemotherapy improves the in vitro anti-tumor activity of mesothelioma

[0184] The oncolytic potency of ONCOS-102 was tested in vitro in three mesothelioma cell lines ( figure 1 A). JL-1 (epithelial mesothelioma), MSTO-211H (malignant biphasic) and H226 (epithelial morphology) cells appear to be relatively resistant to oncolysis, as 10VP / cell (suboptimal dose) in 3 days 18%, 24% and 11% of the cells were killed respectively. JL-1 and H226 cell lines were more resistant to chemotherapy-mediated cytotoxicity compared with MSTO-211H cells (pemetrexed+cisplatin or pemetrexed+carboplatin). Incubation with chemotherapeutics killed only 10% of JL-1 and 11-12% of H226 cells within 3 days. In contrast, at day 3 of co-culture with pemetrexed+cisplatin and pemetrexed+carboplatin, 63% and 73% of MSTO-211H cells were killed, respectively. Combination of ONCOS-102 with chemotherapeutics significantly increased cytotoxicity i...

Embodiment 2

[0186] Example 2. Combination of ONCOS-102 and chemotherapy enhances immunogenic cell death and viral replication in mesothelioma cell lines

[0187] Immunogenic cell death markers, such as calreticulin A exposure to the cell surface and extracellular ATP and HMGB1, were measured from mesothelioma cell cultures after exposure to ONCOS-102, chemotherapeutic agents, or a combination of both. freed( figure 2 ). Treatment with ONCOS-102+ chemotherapy induced the most immunogenic tumor cell death in Jl-1 and H226 mesothelioma, as the highest amounts of CRT exposure and extracellular HMGB1 and ATP were measured in these groups freed. Conversely, in MSTO-211H cells, simultaneous administration of ONCOS-102 and chemotherapy was as immunogenic as chemotherapy alone, consistent with observations from cell viability assays, confirming the high responsiveness of these cells to chemotherapy sensitivity.

[0188] The effect of chemotherapy on the replication of ONCOS-102 in vitro was a...

Embodiment 3

[0189] Example 3.ONCOS-102 shows high tropism for mesothelioma cells

[0190] ONCOS-102 is a chimeric oncolytic adenovirus in which the fiber round head 5 is replaced by the serotype round head 3 domain. Screen positive cells for CD46, DSG2 (Ad3) and CAR (Ad5) receptors ( image 3 B). MSTO-211H, H226 and JL-1 expressed high levels of CD46 (98%, 96% and 98%, respectively), DSG2 (95%, 7% and 64%, respectively) on their surface. CAR receptors were expressed by two of the three types of mesothelioma, H226 (88%) and J11 (15%).

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Abstract

The invention relates to oncolytic adenovirus vector and chemotherapeutic agents. More specifically, the invention relates to oncolytic adenovirus vector and chemotherapeutic agents for use in a cancer therapy. The combination therapy as described herein has superior safety properties and have effective therapeutic activity.

Description

field of invention [0001] The present invention relates to the field of medicine. Specifically, the present invention relates to a novel strategy for the treatment of human cancers using ONCOS-102 adenovirus in combination with two chemotherapeutic agents. Also disclosed is a method of treating malignant mesothelioma using this combination of virus and chemotherapeutic agents. In addition to the virus and the two chemotherapeutic agents, other drugs may also be included in the treatment regimen. Background of the invention [0002] Malignant mesothelioma (MM) is an aggressive and rare form of cancer that develops from the mesothelium. MM is mainly caused by exposure to asbestos and exhibits a long incubation period, usually >30 years. The median survival time of patients with mesothelioma after diagnosis is usually only 9-12 months. MM affects the pleura (the outer lining of the lungs and inner chest wall) in 85.5% of MM cases, the peritoneum (lining of the abdominal ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/86
CPCA61K45/06A61K35/761A61K31/519A61K33/243A61K31/555A61K31/675A61P35/00A61K2300/00C12N15/86C12N2710/10332C12N2710/10343C12N2710/10371A61K33/24A61K31/282A61K31/573A61K31/664A61K31/714A61K48/00C12N15/861
Inventor L·库尔克T·兰基S·佩索宁E·哈维斯托A·沃兰托L·瓦西莱夫
Owner TARGOVAX