A novel targeted treatment against ovarian cancer

Important results from the project

We recently discovered a specific epitope (referred to herein as “t334”-the target) of a monoclonal antibody that blocks a tumour cell-specific target, leading to cell death and reduced tumour growth via a novel cancer pathway. This target belongs to a family of transmembrane serine/threonine tyrosine kinases. The target t334 gene expression was increased in cancer cells compared with normal tissues. The aim now is to develop this new chemical entity (TTX33o) into a treatment for solid tumours, with an initial focus on gynecological cancers.

Expected long term effects

The clinical significance of the candidate gene was analyzed using TMA consisting of 204 stage I and II ovarian tumors, and 450 aggressive stage III and IV ovarian tumors. Cellular localization of the candidate protein was in the nucleus and the cytoplasm but to a larger extent to the nucleus. We observed unfavorable outcome for patients with samples containing high protein expression of the candidate gene in the cytoplasm than in the nucleus. The same pattern of expression is seen breast tumors. Kidney cancers showed candidate gene cellular localization in the cytoplasm and nucleus.

Approach and implementation

Our partners performed the MTD analysis with the peptides produced by Temple and selected two optimal peptides using the ovarian established by InSphero cell- and patient derived xenografts (CDX and PDX). Tumor material was collected for biodistribution and pathological analysis and sent to Sahlgrenska for analysis, tumor samples were embedded in paraffin blocks. The Paraffin blocks were sectioned, and slides were stained with eosin/hematoxylin. In addition, slides were hybridized with the candidate gene antibody. The material was validated by our pathologist in Gothenburg.