Cancer Vaccine - Synthetically generated glycopeptides from tumor cells can stimulate the formation of specific antibodies

Nov 3 2005

Tumor cells and healthy somatic cells differ in the structures on their surfaces. In principle, it should thus be possible to develop a vaccine that causes a patient’s immune system to form antibodies that attack and destroy tumor cells while sparing healthy cells.

Because these differences between surface antigens are often minimal, all efforts in this direction have thus far failed; it has not been possible to elicit a targeted immune response directed exclusively against the tumor cells.

A team of researchers headed by Horst Kunz in Mainz, Germany, has now come a step further. They have successfully developed a synthetic vaccine that induces a strong and specific immune response against the desired tumor antigen in mice.

Required for the production of antibodies is the interplay between two different types of cells, B cells and helper T cells. In the body are individual B cells with a designated binding site for a specific tumor antigen on their surface. In order for these cells to multiply and mature into antibody-producing plasma cells, they must come into direct contact with helper T cells. In preparation for this, they take up the bound tumor protein, digest it, and stick peptides from it, together with a surface protein called the major histocompatibility complex (MHC II), out on their surface. When such a prepared B cell meets up with a helper T cell whose T cell receptor recognizes this peptide exactly, the B and T cells bind to each other by means of a molecular bridge consisting of the T cell receptor, peptide, and MHC. This bond stimulates the T cell to produce growth factors that act on the B cell, causing it to multiply and produce antibodies.

The Mainz chemists synthesized a vaccine from two components: a glycopeptide from a tumor protein and a peptide from chicken egg white, ovalbumin. These were bound together by an amino acid spacer. They used this compound to immunize mice whose T cell receptors recognize the ovalbumin peptide. This had the desired effect; the mice formed antibodies that selectively bound to the tumor antigen but not to similar structures on healthy cells.