Antibody to a molecularly-defined antigen confined to a tumour cell surface

Abstract

TUMOUR-SPECIFIC antigens have usually been demonstrated with little knowledge of their molecular nature; for example by the residual reactivity with tumour shown by an anti-tumour serum which has been absorbed with normal tissue. Certain tumours of B lymphoid cells which secrete immunoglobulin (Ig) provide a promising situation for identification of the antigen in molecular terms^1–3. Amino acid sequences in the variable (V) regions of Ig molecules determine not only antibody activity, but also the ‘idiotypic’ antigenic determinants of the molecule (for review see ref. 4). In a normal B lymphoid clone the V regions on the surface Ig of the early members are the same as those on the Ig exported by specialised protein-secreting descendants and are essentially unique to this clone^5,6. The morphology and mode of Ig secretion in neoplastic cells are frozen at some stage in the range shown by their normally differentiating counterparts (Fig. 1). Tumours with cells having both surface and export Ig have provided Ig in the host serum in amounts suitable for the conventional raising of anti-V sera. These sera, by reacting specifically with the surface Ig of the corresponding tumour, demonstrated that the V regions can represent tumour-specific antigens^2,3. Furthermore, Lynch et al.¹ demonstrated that mice immunised so as to produce antibodies to the V regions of such a tumour (a syngeneic mouse myeloma) were thereby afforded a measure of specific protection against tumour challenge.