Immune responses to all ErbB family receptors detectable in serum of cancer patients

Employing NIH3T3 transfectants with individual human ErbB receptor coding s equences as recombinant antigen sources, we detected by immunoblot analysis specific immunoreactivity against all four ErbB receptors among 13 of 41 s era obtained from patients with different types of epithelial malignancies. Overall, serum positivity was most frequently directed against ErbB2 follo wed by EGFR, ErbB3 and ErbB4, Specificity patterns comprised tumor patients with unique serum reactivity against ErbB2 or ErbB4, Moreover, approximate ly half of the positive sera exhibited concomitant reactivity with multiple ErbB receptors including EGFR and ErbB2, EGFR and ErbB4, ErbB2 and ErbB3 o r EGFR, ErbB2 and ErbB3, Serum reactivity was confirmed for the respective ErbB receptors expressed by human tumor cells and corroborated on receptor- specific immunoprecipitates, Positive sera contained ErbB-specific antibodi es of the IgG isotype. Representative immunohistochemical analysis of tumor tissues suggested overexpression of ErbB receptors for which serum antibod ies were detectable in five of six patients. These findings implicate multi ple ErbB receptors including ErbB3 and ErbB4 in addition to EGFR and ErbB2 in primary human cancer. Heterogeneity of natural ErbB-specific responses i n cancer patients warrants their evaluation in Light of immunotherapeutic a pproaches targeting these receptors.