Artificial Immunity

Research papers p. 405-409

Artificial immunity

Sometimes the body needs a little prompting to heal itself. Scientists think they might have come up with a way of artificially stimulating the immune system into action against tumors and infectious agents using genetic engineering. By introducing human proteins into cultured mouse cells, they have created artificial cells that mimic natural antigen-presenting cells' ability to activate the body's immune system against tumors cells or pathogenic viruses. These artificial antigen-presenting cells are not only much easier to culture and handle than the body's own antigen-presenting cells, they also appear more effective at activating the immune system against influenza and tumor antigens.

The idea behind cellular therapies against cancer or infectious disease is that foreign antigen on the surface of antigen-presenting cells can be used to awaken the immune system's sentinels-cytotoxic T cells-so that they seek out and destroy a tumor or pathogenic agent. Currently, this approach involves the isolation and purificaction not only of cytotoxic T cells that do the killing, but also the antigen-presenting cells required to stimulate them. The problem is that the purification of donated natural antigen-presenting dendritic cells from bone marrow or blood is a labor-intensive process and these cells must be immune matched to the patient's body-that is, contain the same human leukocyte antigen (HLA) type.

Now Michel Sadelain and Jean-Baptiste Latouche have come up with an alternative: They have engineered mouse fibroblast cells to express human HLA class I (A2.1) together with several other accessory proteins-B7.1, LFA-3, and intracellular adhesion molecule 1 (ICAM-1). With assistance from B7.1, LFA-3 and ICAM-1, the HLA class I molecule complex orientates foreign antigen in such a way that it can be recognized by cytotoxic T cells. Thus, artificial antigen presenting cells can be grown in the laboratory and used to stimulate T cells of any patient of a given human leukocyte antigen (HLA) type. When the resultant artificial antigen-presenting cells are loaded with foreign antigen (influenza antigen, tumor antigens MART1, or tumor antigen gp100) and cultured with a patient's cytotoxic T cells, the T cells show potent responses against target cells bearing the foreign antigens, as measured by the release of a radioactive isotope.

The authors suggest that the approach will be very useful for studying the process of cytotoxic T cell activation and in particular for the development of antigen-specific T cells for use in therapies against cancer.

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