Translational molecular biology and immunology of melanoma.
The objective Prof. Markel’s research group is to define robust, clinically-relevant, biological mechanisms of melanoma pathogenesis, and translate the findings into the clinical arena.
1. Identification of tumor immune evasion mechanisms.
Delineation of such mechanisms immediately highlights them as potential candidates for novel drug development. For example, Prof. Markel discovered that the CEACAM1 protein protects melanoma cells from cytotoxic lymphocytes by inhibiting various effector functions. A blocking monoclonal antibody raised against CEACAM1 enhances the killing of melanoma cells by reactive lymphocytes in vitro and inhibits tumor growth in animal models. This type of putative drug can synergize with current modalities. This project was commercialized and currently licensed to cCAM Medical Ltd for further pharmaceutical development.
2. Re-direction of melanoma reactive lymphocytes to metastatic sites.
The success of adoptive transfer of melanoma-reactive lymphocytes depends not only on the potency of the lympohocytes, but also on their ability to track down melanoma cells in vivo. Prof.Markel’s teams study the signature of chemokines secreted by melanoma cells and engineer effector lymphocytes with the appropriate receptors to enhance their ability to migrate towards melanoma cells.