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
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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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