Abstract
Murine monoclonal antibodies directed against tumour associated antigens are potentially useful in tumour diagnosis and therapy. However, all the antigens they recognise may be heterogeneously expressed on tumours and this may allow escape of cells from therapy if a single monoclonal antibody is used. One approach is to use combinations of monoclonal antibodies recognising complementary cell surface antigens. A flow cytometric method which allows accurate quantitation of the intensity of staining and the percentage of fresh primary tumour cells binding a series of monoclonal antibodies has therefore been developed. This allows calculations as the number of drug molecules which could be potentially delivered by each monoclonal antibody and the optimal combination of antibodies which should be used. Monoclonal antibodies recognising Y hapten (C14), CEA (228, 161) and 791T-p72 antigen (791T/36) have been screened as a possible combination for colorectal cancer. There was inter-tumour variation in the binding of all the monoclonal antibodies although combinations could reduce or abrogate this problem. A combination of the monoclonal antibodies C14, 228, 791T/36 and 161 would recognise 100% of tumours. Sixty per cent of tumours bound all four antibodies, 78% any three, 90% any two and 100% any one antibody. There was also intra-tumour variation in the number of tumour cells per lesion that were recognised, the best monoclonal antibody, 161, stained a mean of 59% of cells per tumour whereas the anti-cytokeratin monoclonal antibody stained a mean of 74% of cells per tumour. An increased intensity of staining of tumour membranes was observed when a combination of C14 and 228 was used compared to binding of individual antibodies. Furthermore there was still no significant binding to normal colon membranes. Combinations of monoclonal antibodies which recognise a high percentage of tumours are likely to be necessary for monoclonal antibody drug targeting to prevent tumour recurrence and/or metastases.
Highlights
This is not a new concept very few studies have been published showing that combinations of antibodies recognise a larger number of primary tumours
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
Antibodies to tumour associated antigens A panel of murine monoclonal antibodies were used in this study. 791T/36 is an IgG2b monoclonal antibody which recognises the 791T p72 antigen found in many carcinomas (Embleton et al, 1981; Price et al, 1983)
Summary
This is not a new concept very few studies have been published showing that combinations of antibodies recognise a larger number of primary tumours. Most studies have used either cell lines or human xenografts, neither of which has the heterogeneity observed in human tumours. Our early studies (Durrant et al, 1986a) showed that it was necessary to analyse at least 50 individual colorectal tumours to obtain a clear picture of tumour phenotypes as the intertumour variation was so diverse. In this report we compared the binding of a panel of anti-colorectal monoclonal antibodies reactive with different 'tumour associated' epitopes singly and in combinations, to colorectal tumour cells
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
