Antibodies specific for disease-associated antigens (DAA) expressed in non-malignant diseases reveal potential new tumor-associated antigens (TAA) for immunotherapy or immunoprevention

Abstract

Immune responses to a large number of mutated and non-mutated tumor antigens have been studied in an attempt to unravel the highly complex immune response to cancer. Better understanding of both the effectors and the targets of successful immunosurveillance can inform various immunotherapeutic approaches, which can strengthen or replace natural immunosurveillance that a tumor has managed to escape. In this review we highlight targets of antibodies generated in the context of diseases other than cancer, such as asthma, allergies, autoimmune disorders, inflammation and infections, where the antibody presence correlates either with an increased or a reduced lifetime risk of cancer. We focus on their target antigens, self-molecules abnormally expressed on diseased cells or cross-reactive with exogenous antigens and found on cancer cells as tumor associated antigens (TAA). We refer to them as disease-associated antigens (DAA). We review 4 distinct categories of antibodies according to their target DAA, their origin and their reported impact on cancer risk: natural antibodies, autoantibodies, long-term memory antibodies and allergy-associated antibodies. Increased understanding and focus on their specific targets could enable a more rational choice of antigens for both therapeutic and preventative cancer vaccines and other more effective and less toxic cancer immunotherapies.

Keywords: Autoantibodies; Immunotherapy; Inflammation; Molecular mimicry; Natural antibodies.

Figure 1:. Antibodies made in non-cancer settings and their association with cancer risk.

The figure specifies antibody isotypes, the known target antigens, known functions and correlations of their presence with cancer risk.

Figure 2:

Tumor associated antigens (TAA) that are also disease associated antigens (DAA) on non-malignant tissues.