LFA-1 and ICAM-1 as Drug Targets in Cancer Research

The lymphocyte function-associated antigen-1 (LFA-1) (also known as CD11a/CD18 and L2) is one of numerous integrins found in the human body, but it is unique in that it is only found in leukocytes. Aside from this antigen, its major ligand ICAM-1 (or CD54) has been linked to cancer through the action of lymphocytes and myeloid cells on tumour cells. It's crucial to understand how LFA-1 promotes leukocyte-tumour interactions, as well as the role of ICAM-1 in tumour dynamics, which can be independent of LFA-1 contact. It's also important to note the antigen's significance in B-cell chronic lymphocytic leukaemia. Different roles of both targets will be discussed, and how both LFA-1 and ICAM-1 shows promising next step in pharmaceutical science, being target for multiple diseases.
Lastly, debate on different inhibitors and their structures and properties. Already widely used is Efalizumab, inhibitor that binds to LFA-1 and it is one of the most effective antibody medicines for treating psoriasis, a prevalent skin disease. The crystal structures of the Efalizumab Fab alone and in complex with the LFA-1 alpha I domain will be described, revealing the molecular mechanism of Efalizumab suppression of LFA-1.

Author(s): Karla Kozina

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