• H Juhl, F Helmig, K Baltzer, H Kalthoff, D Henne-Bruns, and B Kremer.
• Klinik für Allgemeine Chirurgie und Thoraxchirurgie, Christian-Albrechts Universität, Kiel, Germany.
• J Surg Oncol. 1997 Mar 1; 64 (3): 222-30.

BackgroundOne reason for the failure of monoclonal antibody (mab) trials in most cancer patients might be the presence of complement resistance factors that inhibit complement dependent cytotoxicity (CDC) and the release of inflammatory mediators (e.g., anaphylatoxins).MethodWe have determined the expression of CD46, CD55, and CD59 in five gastric, three colon, and seven pancreatic human cancer cell lines by immunostaining. The complement activating properties of mabs and conjugates with cobra venom factor (CVF) were studied in a 51Cr-release toxicity assay and in an ELISA to determine the release of C3a.ResultVirtually all tumor cell lines strongly expressed CD46, CD55, and CD59, except KATOIII gastric cancer cells (CD55 and CD59 negative). In accordance with other studies we could confirm that expression of CD55 and CD59 inhibits a complement activation by mabs. Whereas 17-1A was able to induce a cytotoxic complement activation on KATOIII cells, neither a CDC nor an anaphylatoxin release (C3a) was observed on MKN28 cells (strong expression of CD55 and CD59). Conjugation with CVF, a strong activator of the alternative pathway of complement, could partially restore the complement activation by mabs. A 17-1A-CVF conjugate, although still nontoxic, induced the release of the anaphylatoxin C3a on both cell lines. The same observations were made in PancTuI pancreatic cancer cells treated with a conjugate of the mab CA19-9 and CVF.ConclusionsOur study shows that complement resistance is a frequent event in gastrointestinal cancer, limiting the potential of monoclonal antibodies. Mabs, when conjugated with CVF, partially retain complement activating properties by releasing C3a, which in vivo will support a cellular immune response.

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