Enhanced recognition of human colorectal tumour cells using combinations of monoclonal antibodies

Abstract

A variety of monoclonal antibodies reactive with colorectal tumour associated antigens have been described (Steplewski et al., 1982;Herlyn et al., 1979;Lindholm et al., 1983;Durrant et al., 1986a). However, one problem that needs to be solved before monoclonal antibodies can be used effectively for imaging or therapy is the heterogeneity of cell surface antigen expression on tumours (Durrant et al., 1986a;Brattain et al., 1981;Dexter et al., 1981 tissues (Embleton et al., 1981; Price et al., 1983a, b). It has been used extensively for colorectal tumour imaging (Farrands et al., 1982;Armitage et al., 1983) and linked to ricin A chain has been screened in a phase 1 clinical trial (Byers et al., 1989). 228 recognises carcinoembryonic antigen and not normal cross-reacting antigen. Its main normal reactivity is with secretory components of the gastrointestinal tract. It has also been shown to localise in tumours of colorectal cancer patients (Pimm et al., 1986). 161 antibody also recognises CEA but also cross-reacts with NCA. It therefore binds to a number of normal tissues, including liver and kidney tissues and would therefore be of limited clinical value. C14 recognises the Y haptenic blood group antigen which is expressed widely on colorectal cancers and adenomas (Lloyd et al., 1983;Brown et al., 1984;Abe et al., 1986; Durrant et al., 1986a, b;Ernst et al., 1986). Its main reactivity with normal tissues is restricted to secretory epithelial tissues in individuals who secrete blood group substances (Brown et al., 1984 Our results indicate that more colorectal cancers were recognised and the intensity of staining was increased by using combinations of monoclonal antibodies when compared to a single antibody.

The role of CD55 in protecting the tumour environment from complement attack

“…CD55 is expressed on all cells to protect them from bystander attack by complement and is therefore expressed on blood cells, endothelial cells, and surface epithelial cells. CD55 is over‐expressed (2–100‐fold) by a wide range of solid tumours with individual cells expressing 10 5 −10 6 CD55 molecules per cell (11). In colorectal cancer its over‐expression is an indicator of poor prognosis, implying that tumour cells with high levels of CD55 have a selective advantage.…”

Efficacy and selectivity of monoclonal‐antibody‐targeted drugs and free methotrexate in fluorescence‐labelled mixed tumour‐cell monolayer cultures and multicellular spheroids

“…This differential cytotoxicity has hitherto been demonstrated using either separate target cell cultures or separate conjugates prepared with "relevant" and "irrelevant" MAbs. However, neither test situation addresses the possible effects of cellular heterogeneity which exists in vivo, where tumour cells are in contact with normal cells and also exhibit clonal heterogeneity with regard to each other (Durrant et al, 1989b;Brattain et al, 1981). It is important to control for effects on bystander cells and also the effects of bystander cells on target cells, because cellular interactions may modify aspects of tumour-cell behaviour such as metastasis, growth rate and drug sensitivity (Poste et al, 1981;Heppner et al, 1985;Miller et al, 1981;Leith et al, 1987), and this could affect the efficacy of targeted therapy.…”