PharmaMar (MSE:PHM), a biopharmaceutical company specialised in the discovery and development of marine-derived anticancer drugs, has announced that its novel Antibody-Drug Conjugate (ADC) demonstrates strong anticancer activity in vitro and in vivo against tumours expressing HER2 derived from breast, gastric and ovarian cancers. 

The novel ADC MI130004 consists of a new marine-derived tubulin inhibitor (PM050489) that is covalently bound to the HER2 antibody trastuzumab via a non-hydrolysable linker.

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 tumour cells expressing the receptor HER2 in their surface (HCC-194, SK-BR3 and BT-747) or tumour 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 polymerisation, causing disorganisation 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-expresing tumour cells from breast, gastric and ovarian cancers were subcutaneously implanted into immunosuppressed mice to develop tumours 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 tumour shrinkage with complete tumour remissions in all the mice implanted with BT747 breast tumour 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 tumour cells JIMT-1, the two gastric cancer cells Gastric-008 and N87 and the two ovarian cancer cells SK-OV-3 and A2780cis.

Complete tumour 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 tumours was confirmed 24h after treatment by showing mitotic aberrations in tumour cells indicating an anticancer activity mediated by microtubule inhibition and blockade of cell division.

Source: PharmaMar