Biological characterization of a chimeric mouse-human IgM antibody directed against the 17-1A antigen.
Cancer Immunol Immunother
; 30(1): 43-50, 1989.
Article
em En
| MEDLINE
| ID: mdl-2598174
ABSTRACT
A chimeric antibody was constructed in which the murine H- and L-chain variable regions of mAb 17-1A, raised against human colorectal cancer cells, were joined with the human constant mu and kappa regions. Transfection of these constructs into the murine myeloma Sp2/0 resulted in the expression and secretion of a pentameric Ig, designated chimeric 17-1A IgM. The chimeric 17-1A IgM was subsequently compared to a previously described chimeric 17-1A IgG1 for biological activities. Both chimeric mAbs were equally effective (weight basis) in competing against the binding of murine 125I-17-1A to cultures of HT-29 colon carcinoma cells. The calculated association constants for the chimeric 17-1A IgM and IgG1 were 1.63 x 10(8) l/mol and 3.41 x 10(7) l/mol, respectively. Unlike chimeric 17-1A IgG1, the chimeric 17-1A IgM was able to render colon carcinoma target cells susceptible to lysis by both xenogeneic (rabbit) and human complement. The extent of complement-mediated lysis dependent upon chimeric 17-1A IgM was correlated to 17-1A antigen expression on target cells. HT-29 colon carcinoma cells treated with chimeric 17-1A IgM did not directly result in antibody-dependent cellular cytotoxicity by human peripheral blood monocytes. However, chimeric 17-1A IgM greatly enhanced the deposition of C3 on complement-treated HT-29 cells, and concomitant incubation with monocytes resulted in heightened lysis of the tumor cells. The feasibility of enhancing host defense against gastrointestinal malignancies by the administration of this chimeric 17-1A IgM may have certain clinical advantages.
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Base de dados:
MEDLINE
Assunto principal:
Imunoglobulina M
/
Neoplasias do Colo
/
Anticorpos Monoclonais
/
Antígenos de Neoplasias
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
1989
Tipo de documento:
Article