New HS44 molecule inhibits lung metastasis

One type of white blood cell, the Natural Killer T Cells, fights against infections and tumours by freeing cytokine proteins which activate the body's immune response and destroy infected or malignant cells. To do so they must receive an activation signal. Specific receptors located on their surface act as switches: they activate the lymphocyte in presence of an antigen, a molecule which triggers alarm signals.

With the aim of further strengthening this immune response artificially, scientists have worked with a glycolipid known as the alfa-galactosylceramide, extracted from an isolated molecule found in the marine sponges Agelas mauritianus. Glycolipids join onto receptors and trigger an immunological response, although therapeutical results in clinical trials have not been positive enough. The glycolipid is too powerful and activates white blood cells at a frenetic pace, causing an uncontrollable storm of cytokines. Although this does not affect the health of patients, neither does it reveal a suitable amount of antitumour activity or therapeutic effects.

Researchers at the UAB Institute of Biotechnology and Biomedicine, led by lecturer Raúl Castaño, in collaboration with Amadeu Llebaria, research at the CSIC Institute of Advanced Chemistry, and with the participation of scientists from the Carlos III Health Institute, the University of Southern California and the La Jolla Institute for Allergy and Immunology, have designed and synthesised a molecule resembling the alfa-galactosylceramide, but with minor changes in its structure which modify its behaviour.

The molecule, named HS44, attaches well to the iNKT lymphocyte receptors, but has a faster dissociation. This reduces its strength and allows its activation of the immunological response to be more efficient and controlled. The new HS44 molecule was tested in mice after transferring an aggressive melanoma which produces metastasis in the lungs, a model for the study of human cancer. The results were conclusive: the molecule inhibits lung metastasis. It additionally reduces the possibility of stimulating a potentially harmful self immune response in the organism and, depending on administration, can trigger an adequate immune response to the treatment of microbial infections as an adjuvant vaccine.