Efficacy of MSLN-specific and non-specific monoclonal antibody-chelators-Thorium-227 in tumorbearing nude mouse in combination with checkpoint inhibitors
The thorium conjugate research aims to develop products based on an alpha-pharmaceutical platform with a targeted approach for treatment of cancer. The technology involves connecting the alpha-emitter thorium 227 (Th-227) to tumor targeting antibodies, to form so called Targeted Thorium Conjugates (TTCs). The mechanism of TTCs is based on the unique properties of elements that emit alpha particles. The alpha particles possess high energy and have a short range in biological tissue and therefore have great potential for inducing localized damage to cancer cells with minimal effect on normal cells. The TTCs deliver the therapy to the solid tumor. In this manner, tumors that express the specific target are exposed to the radioactive decay of 227Th.
In this study we aim to investigate efficacy of TTC combined with DNA repair inhibitor - Olaparib - in ovarian cancer. In total we will use up to 250 female athymic nude mice for this study. We will use 60 tumor-bearing animals for evaluation of the in vivo cell damage and up to 100 tumor-bearing animals for the evaluation of efficacy of the combined TTC-inhibitor treatment. As the tumor growth rate is below 100% we applied for 250 animals in this study, but most probably wil use much fewer animals. Extensive in vitro studies were performed to identify the model cell lines and drug combinations, as well as the efficacy of this drugs, so that the chance for success is high. We also constantly improving our techniques, hence the technical part of the study is not challenging and we have long experience with similar studies.
In this study we aim to investigate efficacy of TTC combined with DNA repair inhibitor - Olaparib - in ovarian cancer. In total we will use up to 250 female athymic nude mice for this study. We will use 60 tumor-bearing animals for evaluation of the in vivo cell damage and up to 100 tumor-bearing animals for the evaluation of efficacy of the combined TTC-inhibitor treatment. As the tumor growth rate is below 100% we applied for 250 animals in this study, but most probably wil use much fewer animals. Extensive in vitro studies were performed to identify the model cell lines and drug combinations, as well as the efficacy of this drugs, so that the chance for success is high. We also constantly improving our techniques, hence the technical part of the study is not challenging and we have long experience with similar studies.