Technologies

UCLA researchers have developed a new product for the detection, prognosis and prediction of multiple cancers based on the simultaneous detection of serum antibodies to multiple tumor-associated antigens. The method bypasses the expensive and difficult requirement for purification of individual recombinant TAA proteins by using chemically synthesized peptides of the TAA.

BACKGROUND

Detection of serum-derived antibodies against microbial antigens is routinely used for the diagnosis and prognosis of some infectious diseases. In the past 10 years, strong evidence has emerged to support the theory that the human immune system also mounts spontaneous humoral responses against autologous tumor-associated antigens (TAA). Up to now, there are at least 1800 TAA identified based on recognition by antibodies present in patients sera. These TAA include targets from many cancer types, such as melanoma, renal cancer, Hodgkins disease, esophageal cancer, lung cancer, colon cancer, gastric cancer, breast cancer, prostate cancer and so on.The discovery of these TAA awakens the old hope of finding serological markers for cancer detection, diagnosis and prognosis. However, the development of a sensitive, cost effective and comprehensive cancer diagnostic based on serological profiles to TAA has been limited by practical problems. For example, most of the antigens react with few - or no -- allogeneic sera. This indicates that an effective diagnostic for a given cancer must test for the presence of antibodies to a large number of TAA associated with that cancer. Such a test would require the recombinant production and purification of multiple TAA proteins, which is expensive and difficult to achieve. Multiplying these problems by each cancer for which a screen is desired makes developing a comprehensive test unfeasible.What is needed is a platform solution that enables the sensitive detection of serum antibodies to multiple TAA for multiple cancers.

INNOVATION

The present invention enables the creation of a new product for the detection, prognosis and prediction of multiple cancers based on the simultaneous detection of serum antibodies to multiple TAA. The method bypasses the expensive and difficult requirement for purification of individual recombinant TAA proteins by using chemically synthesized peptides of the TAA. Utilizing prediction software, researchers at UCLA have demonstrated that one can systematically and efficiently predict peptide regions on a TAA that can (1) react to antibodies in a subset of patients with a specific cancer, and (2) effectively distinguish a cancer patient from a negative control as accurately as the recombinant TAA. This approach of using peptide fragments of TAA to detect their corresponding antibodies in a patients serum can be repeated with any number of TAA to create a panel array of synthetic peptide fragments to provide a sensitive and comprehensive test for multiple cancers.

The UCLA researchers have proven the feasibility of the approach by using their prediction software to identify a peptide fragment of NY-ESO-1, a tumor associated antigen highly expressed in different types of cancers. NY-ESO-1-specific antibodies present in the sera of patients with melanoma, prostate cancer, non-small cell lung cancer, esophageal cancer, gastric cancer, and hepatocellular carcinoma reacted with the synthetic peptide at a frequency similar to their reaction with the recombinant protein. This proof-of-principle demonstrates the feasibility of applying the same methodology to multiple TAA to create an entirely new product line of synthetic TAA fragments for the routine detection, prognosis and prediction of multiple cancers.The UCLA investigators would welcome the opportunity to collaborate with an industrial partner for the continued identification and validation of reactive fragments to other TAA. The UCLA researchers can bring to this collaboration two valuable assets: Know-how in identifying peptide fragments for use in serological detection of cancer; and access to clinical samples and clinical data in different cancer indications.

RELATED MATERIALS

Dominant B cell epitope from NY-ESO-1 recognized by sera from a wide spectrum of cancer patients: Implications as a potential biomarker. Int J Cancer. (2005)