The Test is Based On Auto-Antibodies Against a Tumor-Associated Non-human Sugar Which Could Also Serve as an Immunotherapy Target
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(HealthNewsDigest.com) – Vista, CA. – Scientists at Sialix Inc., a glycomics firm in Vista, CA, report that they have a glycan microarray-based test that could be useful in detecting breast cancer from a simple blood serum sample. The sialic acid glycan microarray test detects the body’s immune response to tumor-associated sugar chains that contain a non-human glycan. The work, reported in the May issue of Cancer Research (Padler-Karavani, Hurtado-Ziola, et al., Cancer Res., May, 2011), screened sera from 386 cancer cases and was done in collaboration with the two UCSD investigators, Dr. Richard Schwab of the UCSD Moores Cancer Center, and Dr. Ajit Varki, of the UCSD School of Medicine.
The microarray has 40 different sialic acid glycan chains aimed at identifying antibodies against a non-human sialic acid called N-glycolylneuraminic acid (Neu5Gc). A tumor-associated glycan, sialyl Tn (S-Tn) has long been found in abnormal cell growth such as carcinomas. During the study, serum antibodies against the Neu5Gc-form of S-Tn (Gc-S-Tn) were found in many of the breast cancer patients. Finding S-Tn as one of the glycan chains recognized by antibodies in patients with breast cancer could have been predicted because S-Tn has often been considered a cancer-specific glycan. Sialix Inc., under an exclusive licensing agreement with UCSD, is expanding the research findings as it is currently performing a 400-patient trial using serum samples provided by the National Cancer Institute’s Early Detection Research Network under an NCI Phase II funding mechanism.
Red meat and other animal-derived foods such as dairy products are rich in Neu5Gc and is the primary source of this non-human sialic acid. The incorporation of Neu5Gc into tumor-associated glycans such as S-Tn is another modification often seen in specific types of cancer cells. Neu5Gc differs from the human form of the sialic acid Neu5Ac by a single oxygen atom. During metabolic processes, the body treats structurally similar Neu5Ac and Neu5Gc the same and incorporates them into human tissue and cell surfaces. However, the human immune system does not recognize Neu5Gc, sees it as foreign, and thus a danger. The immune system responds by producing antibodies against Neu5Gc. It is the combination of Gc-S-Tn and Gc-S-Tn antibodies that could serve as a cancer biomarker and possibly as a treatment.
In another part of the study researchers examined the use of Neu5Gc as a target for immunotherapy using human antibodies against Gc-S-Tn as a treatment. The human anti-Gc-S-Tn antibodies were purified from IGIV, an concentrated antibody preparation that is made from pooled human serum. IGIV is clinically available and used in the treatment of immune disorders. The rationale behind this type of treatment is this – the immune system will attack that which it considers foreign or dangerous, sometimes including its own tissues and cells. If the antibody level against Gc-S-Tn is high enough, as it would be when it is purified from IGIV, it will cause the immune system to initiate the killing of cells that have Neu5Gc on their surface in order to rid the body of potentially dangerous cells. The UCSD collaborators were able to demonstrate just that in a mouse using mouse carcinoma cells that have Neu5Gc. The mice injected with carcinoma cells were treated with purified human anti-Neu5Gc antibodies, some of which were presumably against Gc-S-Tn. The outcome was that the carcinoma growth was attenuated when compared with mice that were not treated with purified anti-Neu5Gc antibodies.
Although further work and testing would need to be done in order to bring such a treatment and diagnostic test to the clinic, this type of immunotherapy does seem feasible. The presence of Gc-S-Tn has also been found in other types of cancer such as prostate and colon cancer. Although the early data from the current 400-subject trial using the newly expanded microarray suggests that a multi-marker approach could prove more effective, the study would need to be completed including the statistical examination of the entire dataset before we can really begin moving the unusual biomarker and immunotherapeutic treatment through the FDA. Should the findings continue to be positive it is anticipated that the sialic acid glycan microarray could be the first product available from these findings.
Dr. Nancy Hurtado-Ziola – Senior Scientist and Principal investigator, Sialix Inc.
Dr. Hurtado-Ziola earned a doctoral degree in Biomedical Science from the UCSD School of Medicine in 2007. As a Ph.D. graduate student in the laboratory of Dr. Ajit Varki, the focus of her work was to compare the expression and binding patterns of a specific sub-family of hominid proteins found in the immune system – the Sialic acid-binding ImmunoGlobulin-like lectins, called Siglecs. Although humans, chimpanzees and bonobos are genetically quite similar, she found species-specific differences in Siglec expression patterns and Siglec sialic acid binding specificities. After a brief post-doctoral fellowship at UCSD, she was recruited to be the first scientist at Sialix Inc., which at the time was known as Gc-Free, Inc. Currently, Dr. Hurtado-Ziola is involved in multiple NIH-funded projects at Sialix, and she was instrumental in the collaborative effort to design and produce the sialic acid glycan microarray that may likely become a diagnostic tool in the fight against cancer.
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