ABSTRACT
Summary The analysis of the B-cell repertoire against tumors using tumor cDNA expression cloning and autologous serum by serological analysis of antigens by recombinant expression cloning (SEREX) revealed that many, if not all, human tumors express multiple antigens which are recognized by the patient’s immune system. There are different antigen specificities: (1) shared tumor antigens, (2) differentiation antigens; products of (3) mutated, (4) viral, (5) overexpressed and (6) amplified genes, as well as (7) splice variants of normal genes, (8) widely expressed autoantigens, the immunogenicity of which is restricted to cancer patients, (9) common autoantigens, to which antibodies are found in the sera from patients with other than malignant diseases; and finally (10) products of genes which are underexpressed in the autologous tumor compared to normal tissues. Our results indicate that the context of presentation of a molecule is more important for its immunogenicity than its more or less restricted expression in tumors. This implies that only immunotherapeutic approaches based on specific antigens are likely to induce tumor-specific reactions, whereas whole-tumor cell approaches would rather induce tolerance and/or autoimmune disease. CD8 as well as CD4 responses could be demonstrated against SEREX antigens and the relevant antigenic peptides have been defined. With the availability of specific antigens for the majority of human cancers, carefully designed trials have to be performed to determine the value of our knowledge about these antigens for immuno-and genetherapeutic approaches in patients with malignant disease.
