Augmented Lung Adenocarcinoma Cytotoxicity by the Combination of a Genetically Modified Anti‐Lewis Y Antibody and Antibodies to Complement Regulatory Proteins

A. AZUMA, Y. YAMANO, A. YOSHIMURA, T. HIBINO, T. NISHIDA, H. YAGITA, K. OKUMURA, T. SEYA, R. KANNAGI, M. SHIBUYA, S. KUDOH

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Complement‐dependent cytotoxicity (CDC) mediated by a chimeric anti‐Lewis Y monoclonal antibody (cH18A; human IgGl) was investigated in this study. Human lung adenocarcinoma cell lines (PC7, PC9, and PC 14) were used as the target cells. PC7 and PC9 cells, expressed Lewis Y antigen and were lysed by cH18A as effectively as by the parent mouse anti‐Lewis Y antibodies (mH18A) in a concentration‐dependent manner. PC14 cells did not express Lewis Y antigen and were not lysed by either cH18A or mH18A. cH18A mediated CDC activity against PC7 and PC9 cells was enhanced by the combined use of monoclonal antibodies directed against CD46(MCP), CD55(DAF), and CD59. These molecules are complement‐regulatory proteins which protect host cells from CDC. PC7 and PC9 cells, showed high levels of surface expression of these proteins, PC7 cells were more susceptible to cH ISA‐mediated CDC than PC9 cells. Use of multiple blocking antibodies to the complement‐regulatory proteins produced more enhancement of cH18A‐mediated CDC than a single antibody. Moreover, expression of CD55 and CD59 by PC7 and PC9 cells was decreased after treatment with Pl‐PLC, resulting in increased susceptibility to cHISA‐mediated CDC. Although the reason is unknown, PC7 cells became more susceptible to CDC than PC9 cells after PI‐PLC treatment even in the absence of cH18A. These data suggest that chimeric monoclonal antibodies can be used to induce CDC against lung adenocarcinoma, and that such CDC is potentiated by a variety of antibodies blocking compliment‐regulatory proteins on the tumour cell surface.

Original languageEnglish
Pages (from-to)202-208
Number of pages7
JournalScandinavian Journal of Immunology
Volume42
Issue number2
DOIs
Publication statusPublished - 1995 Aug
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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