Simultaneous Vascular Targeting and Tumor Targeting of Cerebral Breast Cancer Metastases Using a T-Cell Receptor Mimic Antibody.

摘要

The goal of the project is to demonstrate uptake and therapeutic effect of a specific monoclonal antibody, RL6A, by brain metastases of human breast cancer cells in a mouse model. As described in the previous annual report, both the immune compromised NOD/Scid/Il2R (= NSG), HLA-A2 transgenic mouse strain and the non-transgenic NSG control strain develop metastatic tumors in peripheral organs after intracardiac (left ventricular) administration of tumor cells. We have subsequently explored the use of intracarotid artery administration. However, even though CD1 mice used in pilot intracarotid injection experiments all tolerated unilateral occlusion of the common carotid artery (necessary to avoid bleeding after injection), most of the mice from NSG strains (JAX 5557 and 9617) died during or shortly after the procedure. Therefore, we are currently conducting a series of stereotaxic intracranial injections. As a second alternative we have initiated the custom breeding of novel HLA-A2 transgenic mice on a nude/nude background, which should avoid the problem of peripheral metastases seen with NSG mice.