A cytotoxic molecule in an inactive formulation is attached to an antibody. The prodrug is attached via what is known as a hindered disulfide bond, Sayare says. This is a covalent bond that is broken inside the cell via reduction. Once the bond is broken, the toxin is released and kills the cell. ImmunoGen's current payload of choice is maytansine, which inhibits polymerization of tubulin into microtubules.
Microtubules perform vital functions such as separating chromosomes during mitosis.
It's in the same chemical class as the cancer drug Taxol. Other toxins could be used, Sayare says, as long as the conjugated antibody is nontoxic and the toxicity is only produced inside the target cells, which means the conjugate must be taken inside the cell. More and more companies have come to recognize that our technology platform is enabling. Naked monoclonal antibodies, with the possible exception of Rituxan and maybe Herceptin, probably do not work as effectively against cancer cells as a monoclonal antibody that has an effector molecule attached. We've done this with 17 different antibodies.