Synergy of ricin A chain-containing immunotoxins and ricin B chain-containing immunotoxins in in vitro killing of neoplastic human B cells.

AUTOR(ES)

Vitetta, E S

RESUMO

A strategy is described for improving the efficacy of ricin A chain-containing immunotoxins. Highly purified preparations of ricin A chain or ricin B chain were separately coupled to anti-human immunoglobulin antibodies and the conjugates (immunotoxins) were affinity purified to eliminate free chains. Mixtures of anti-Ig-A and anti-Ig-B immunotoxins markedly synergized in vitro in their ability to kill the Ig-bearing human lymphoma cell line Daudi. In contrast, A-chain- or B-chain-containing immunotoxins of irrelevant specificity did not synergize with anti-Ig-A or anti-Ig-B immunotoxins. This finding indicates that free A or B chains do not play a major role in the synergy and that the synergy is specific. Thus, synergy depends on the specificity of the two antibodies; the lectin binding ability of a B-chain-containing immunotoxin of irrelevant specificity does not suffice. This approach of delivering ricin A chain and B chain separately to a target cell may have significant advantages in killing cells that are not effectively killed by A-chain-containing immunotoxins alone.

Documentos Relacionados

• Selective cytotoxicity of ricin A chain immunotoxins towards murine cytomegalovirus-infected cells.
• Selective killing of normal or neoplastic B cells by antibodies coupled to the A chain of ricin.
• Natural killing of tumor cells by human peripheral blood cells. Suppression of killing in vitro by tumor-promoting phorbol diesters.
• Interleukin 6 gene expression in normal and neoplastic B cells.
• Biosynthesis in vitro of fucose-containing glycosphingolipids in human neuroblastoma IMR-32 cells.