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One way to improve the therapeutic index of anti-cancer agents would be to target them to the tumour site, thereby sparing normal tissues. Tumour targeting approaches heavily rely on the availability of specific binding molecules, recognising markers which are selectively expressed in the tumour environment. The display of antibody repertoires on the surface of filamentous phage, together with efficient selection-amplification schemes, allows the isolation of good-quality human antibodies against virtually any molecular target. This article illustrates how antibody phage technology has been used in our laboratory for the isolation of tumour targeting agents. Furthermore, we present recent developments in the display of repertoires of small globular proteins on filamentous phage, aimed at the isolation of specific binding molecules with molecular weight < 10000 Dalton.

Monoclonal antibodies, which recognise markers of the modified tumour extracellular matrix, may be valuable tools for the diagnosis and therapy of cancer. The pattern of expression of some good-quality tumour-associated antigens is known to be regulated by intracellular pH. In this article, a strategy is described for the isolation of human antibodies specific for proteins which are differentially secreted by fibroblasts at different pH values. We panned a large synthetic antibody phage library against biotinylated proteins secreted by normal human dermal fibroblasts, cultured at pH 7.5, in the presence or in the absence of a molar excess of unbiotinylated proteins, secreted by fibroblasts cultured at pH 6.7. A panel of monoclonal antibodies was isolated, whose reactivity was tested by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry.