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Cooperation of IgG Monoclonal Antibodies in Macrophage Antibody‐Dependent Cellular Cytotoxicity (ADCC) to Tumor Targets
Author(s) -
Ralph Peter,
Nakoinz Ilona
Publication year - 1984
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.35.1.131
Subject(s) - antibody dependent cell mediated cytotoxicity , monoclonal antibody , antibody , microbiology and biotechnology , biology , antigen , antiserum , cytotoxicity , immunoglobulin g , monoclonal , immunology , in vitro , biochemistry
Six IgG monoclonal antibodies representing the four murine IgG isotypes were active individually in ADCC to T‐lymphoma targets mediated by murine macrophages and human blood K cells. The monoclonals were directed against four antigens (Thy‐1.2, H‐2 k , Ly 2.1, Ly 9.2). None was as effective in ADCC as allo‐anti‐Thy‐1.2 serum or rabbit anti‐mouse spleen serum, even at plateau levels of killing. Monoclonals gave the highest levels of ADCC at relatively low amounts of antibody bound to targets; increasing the amount of bound antibody by 10‐ to 100‐fold did not increase murine macrophage‐mediated cytotoxicity. In contrast, ADCC using alloantiserum continued to increase over the same range of antibody bound to the tumor targets. The activity of individual monoclonals was not enhanced by the presence of various dilutions of normal mouse or rabbit serum, suggesting that the superiority of the allo‐ and heteroantisera was due to their content of heterogeneous antibodies. IgG monoclonls of different isotypes and recognizing different antigens gave enhanced ADCC in combination; monoclonals to the same antigen did not. An IgM anti‐Thy‐1.2 monoclonal was inactive in ADCC and inhibited the activity of IgG monoclonals of the same specificity. These studies show that IgG antibodies of different specificity and class can collaborate in ADCC, and that this cooperative effect is not due simply to increased amounts of antibody bound to the tumor targets.