The failure to identify
biomarkers of clinical significance for
cancer diagnosis and prognosis generated a great deal of skepticism in regard to the usefulness of
autoantibody-based methods. SEREX was a major advancement in immunoscreening that resulted in the identification of a large group of
autoantigens recognized by
cancer sera. However, few SEREX-defined
autoantigens have proven to have definitive diagnostic value in clinical practice. Often, the identified
antigens are patient-specific rather than
tumor-specific and many
tumor-associated
antigens are rare in expression libraries made from non-autologous cells. Since
autoantibodies are part of the normal immune response, it can be difficult to single out
tumor-associated
antibodies from the scores of irrelevant patient-specific responses. In our view, any practical approach for identifying
cancer-related
autoantigens must include an integral strategy for demonstrating
tumor relevance early in the screening process. Care must also be taken not to exclude potentially important
autoantibodies by pre-screening manipulations to patient sera. We have introduced substantial modifications in SEREX, designed to minimize confounding effects of unrelated
autoantibodies and to eliminate steps that preclude the identification of
cancer-related
autoantigens commonly recognized by
cancer sera. In addition, we incorporate methodology to identify candidate
antigens that have potential diagnostic or prognostic value prior to their molecular cloning and characterization.