Date: 2015-11-06
Type of information: Presentation of results at a congress
phase: preclinical
Announcement: presentation of results at the AACR-NCI-EORTC International Conference “Molecular Targets and Cancer Therapeutics” in Boston, November 5-9.
Company: PharmaMar (Spain)
Product: MI130004
Action
mechanism: antibody drug conjugate/ADC. PM050489 is a tubulin-binding agent originally isolated from the marine sponge Lithoplocamia lithistoides. This compound binds with very high affinity to ?-tubulin at a new site, disrupting the microtubule network and impairing its function during divison, which leads to mitotic aberrations. MI130004 is a novel antibody-drug conjugate formed by PM050489, a non-hydrolysable linker and trastuzumab.
Disease: HER2-expressing tumors
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On November 6, 2015, PharmaMar announced that its novel Antibody-Drug Conjugate (ADC) demonstrates strong anticancer activity in vitro and in vivo against tumors expressing HER2 derived from breast, gastric and ovarian cancers (MI130004, a new ADC with a payload of marine origin shows outstanding activity against HER2-expressing tumors - Abstract A147). The results have been presented in a poster presentation during the Therapeutic Agents - Biological session at the AACR-NCI-EORTC International Conference “Molecular Targets and Cancer Therapeutics” taking place in Boston, November 5-9.
When tested in a panel of tumor cells expressing the receptor HER2 in their surface (HCC-194, SK-BR3 and BT-747) or tumor cells that do not express it (MCF-7 and MDA-MB-231), MI13004 demonstrated strong potency in those cells expressing the receptor. The authors found that the ADC MI130004 impairs tubulin polymerization, causing disorganization of the microtubule network leading to mitotic failures and halting cell division in cells expressing HER2, similar to the effect of the payload PM50489.
In the study, HER2-expressing tumor cells from breast, gastric and ovarian cancers were subcutaneously implanted into immunosuppressed mice to develop tumors up to certain volume (about 114 mm3). Upon treatment with MI130004 at different doses once a week over a course of 5 weeks, mice treated with the highest dose showed substantial tumor shrinkage with complete tumor remissions in all the mice implanted with BT747 breast tumor cells that lasted up to 120 days. MI130004 was shown to induce complete remissions in some of, but not all, the mice implanted with the breast tumor cells JIMT-1, the two gastric cancer cells Gastric-008 and N87 and the two ovarian cancer cells SK-OV-3 and A2780cis. Complete tumor remissions lasted even 385, 354 and 341 days in mice implanted with SK-OV-3, Gastric-008 and A2780cis, respectively. The effect of MI130004 in all HER2-expressing tumors was confirmed 24h after treatment by showing mitotic aberrations in tumor cells indicating an anticancer activity mediated by microtubule inhibition and blockade of cell division.
