Targeting high numbers of long-lived Natural Killer cells with high effector function to Malignant Melanoma

Targeting high numbers of long-lived Natural Killer cells with high effector function to Malignant Melanoma

Malignant melanoma is the most aggressive skin cancer and patients suffering from advanced stage melanoma are still faced with an extremely bad prognosis. Malignant melanoma often loses expression of MHC class I and also expresses ligands for activating NK cell receptors. Therefore, melanoma represents a promising target for NK cell based therapy. In several studies, high numbers of tumor-infiltrating NK cells correlated with a good prognosis for cancer patients. Accordingly, it is a challenge for the design of NK cell-based therapies to attract high numbers of NK cells with high effector potential to the tumor tissue. To this end, we address the following aims: i.) Manipulation of chemokines and endothelial adhesion molecules to increase the numbers of endogenous or adoptively transferred NK cells in melanoma tissue ii.) Design of protocols to yield high numbers of long-lived NK cells with high effector potential that accumulate in the tumor for adoptive transfer and iii.) Development of combination therapies to obtain high numbers of NK cells in the melanoma tissue correlating with improved prognosis. This study is performed in close collaboration with Prof. Dr. med. Enk, the Head of the Department of Dermatology, University Hospital Heidelberg. The knowledge gained by the proposed study should serve as a basis for a rational design of NK cell-based therapies against melanoma and other solid tumors.

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