A cancer marker and treatment in one?

Researchers at the University of California, San Diego School of Medicine say antibodies to a non-human sugar molecule commonly found in people may be useful as a future biomarker for predicting cancer risk, for diagnosing cancer cases early and, in sufficient concentration, used as a treatment for suppressing tumor growth.

Ajit Varki, MD, professor of medicine and cellular medicine.

The work was led by Richard Schwab, MD, assistant clinical professor of medicine, and Ajit Varki, MD, professor of medicine and cellular and molecular medicine, with other faculty at the UCSD Moores Cancer Center and the UCSD Glycobiology Research and Training Center. Collaborators include researchers from the groups of Xi Chen at UC Davis, Inder Verma at the Salk Institute and scientists from Sialix, Inc., a biotechnology company based in Vista, CA.

It is published in the April 19 online issue of the journal Cancer Research and in the May 1 print edition.

Every animal cell is cloaked in complex molecules called sialic acids that serve as vital contact points for interaction with other cells and the surrounding environment. Humans produce a particular kind of sialic acid called N-acetylneuraminic acid (Neu5Ac), but can also carry another non-human type called N-glycolylneuraminic acid or Neu5Gc, which is obtained through the diet, notably by the consumption of red meat. The molecular structures of these sialic acids differ by just a single oxygen atom, but this difference is enough to prompt the human immune system to produce a complex anti-Neu5Gc response.

In previous research, Varki and colleagues described how low-dose anti-Neu5Gc antibodies can lead to chronic inflammation, an immunological response associated with cancer development and growth. In the new work, using a novel sialoglycan-microarray, the team discovered that patients with carcinomas have elevated levels of antibodies to one specific Neu5Gc-containing sugar chain. This unusual antigen arises from dietary Neu5Gc incorporation into the cancer marker Sialyl-Tn. It is the first example of a biomarker in the form of human "xeno-autoantibodies" to a dietary molecule.

Following up on this discovery, the scientists also found that purified human anti-Neu5Gc antibodies have immunotherapeutic potential: they specifically kill Neu5Gc-expressing mouse or human tumors when applied at higher concentrations. These findings point to a dual response of anti-Neu5Gc antibodies that can either stimulate tumor growth at a low dose (serving as a biomarker of disease) or suppress tumor growth at a high dose.