Simultaneous Vascular Targeting and Tumor Targeting of Cerebral Breast Cancer Metastases Using a T-Cell Receptor Mimic Antibody
Annual rept. 1 May 2012-30 Apr 2013
TEXAS TECH UNIV HEALTH SCIENCES CENTER LUBBOCK
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The project is based on the generation of metastatic brain tumors using a brain selective cell line, 231-BR, derived from human breast cancer. Therefore, the experimental model to be used must be immune compromised. The other requirement we have for this project is that the experimental animals express human HLA-A2 complexes major histocompatibility complex class I. The antibody we want to evaluate as a potential therapeutic agent is a T-cell receptor mimic restricted to human HLA-A2. Therefore, we must use HLA-A2 transgenic mice. In experiments conducted to date the mouse strain, which fulfills both requirements, JAX 9617, and the corresponding non-transgenic control strain, 5557, were receptive for tumor growth not only in brain, but in a number of peripheral organs e.g. lung, liver, spleen. To avoid the confounding influence of peripheral metastases, we currently explore alternative methods to generate brain tumors intracarotid injections, stereotaxic brain implantation. Regarding the analytical side, we have established an immunoradiometric assay for the RL6A antibody with high sensitivity. In saturation and in competition experiments, radioiodinated RL6A and unlabeled antibody showed a Kd value of 1.16 nM and a Ki of 1.26 nM, respectively.
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