Innovations: Cancer vaccines made to order: Antigenics L.L.C.

Abstract

Antigenics is in a crowded field (Table 1Table 1), but its methods are unique. “The whole Antigenics approach is based on the idea that each person’s cancer has its own antigenic signature,” says cancer immunologist Drew Pardoll (Johns Hopkins University, Baltimore, MD). “In most mouse models that seems to be the case. The jury is still out for human cancer.”Other companies are immunizing with specific antigens, but “ultimately the antigens that will be most useful have not really been identified,” says Pardoll. “Most of the vaccines in play don’t use true tumor-specific antigens,” he says, relying instead on tissue-specific antigens, or antigens from viruses associated with the cancer. In fact, Pardoll says, “true tumor-specific antigens are unlikely [to exist]. But the prospects for getting antigens that are highly expressed in tumors are pretty good. I’m optimistic there will be a pretty good [therapeutic] window.”Genzyme Molecular Oncology (Framingham, MA) is using high-throughput methods to identify promising antigens — after harvesting T cells from tumors they test the T cells for binding to a combinatorial library of peptides. Bruce Roberts, Genzyme’s senior director for gene therapy, agrees that the search for specific mutations is largely a waste of time. “I think the thing that is more reliable is the upregulation of proteins,” he says. “Cancer cells will figure out a way to switch on a protein that will give them a growth advantage,” he says, and the poor regulation of that switch can create an excellent target. Thus the Her2 protein is found in normal epithelial cells, but its gross overexpression in some breast cancers makes the tumors susceptible to Herceptin, a humanized monoclonal antibody made by Genentech, Inc. (South San Francisco, CA).Perhaps there are single antigens that will make good targets, and perhaps the only viable approach will be individualized therapy. For the consumer, at least, it is heartening that both approaches are being pursued vigorously.