Immunologic approaches to inhibiting cell-surface-residing oncoproteins in human tumors

The erbB family of receptor tyrosine kinases are growth factor receptors that are overexpressed or mutated in a large variety of human cancers. Studies of erbB-mediated signal transduction will lead to an understanding of the role played by this family of receptors in normal and transformed cells. In this article, we discuss the contemporary understanding of the structure and function of these receptors, and how these features might be exploited in immunologic strategies of receptor-based growth inhibition. The first part of this article details the structure of erbB receptors as it relates to the process of transformation of cells and the malignant phenotype in human tumors. In the second part of this article, we discuss immunologic approaches to therapy for cancers in which surface-residing erbB receptors are overexpressed or mutated, with an emphasis on studies targeting the p185(neu/c-erbB2) oncoprotein. The potential for antireceptor immunity and the evolution of small molecules for receptor-based immunotherapy are discussed. These studies provide a basis for the application of receptor-based strategies of growth inhibition in erbB-expressing human cancers.