Targeting TEMs in Preclinical Tumor Models

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

The tumor associated stroma plays a vital role in promoting tumor growth and metastasis of solid tumors. Targeting the endothelial cells that line tumor blood vessels and cancer associated fibroblasts is a promising anticancer strategy. We have identified several cell surface tumor endothelial markers (TEMs) that are promising targets for anticancer therapy. Several agents targeting the TEMs we discovered are now in clinical trials. To target cell surface TEMs, we have developed antibodies that recognize native TEM proteins on the cell surface of both mouse and human tumor vessels. In initial studies antibodies are selected for their ability to bind live cells which express the target TEM. Whenever possible, secondary screens are used, for example, to identify neutralizing antibodies. Subsequently, antibodies with the best sensitivity and specificity are tested for tumoricidal properties in preclinical mouse models and, if necessary, may be conjugated to small molecular weight drugs to generate antibody-drug conjugates. CAR T cells and bispecific antibodies will also be generated. Combinations of our novel anti-angiogenics with checkpoint inhibitors will also be tested.