ANTIBODY-PSEUDOMONAS EXOTOXIN-A CONJUGATES CYTOTOXIC TO HUMAN-BREAST CANCER-CELLS INVITRO

  • 1 July 1986
    • journal article
    • research article
    • Vol. 46  (7) , 3262-3267
Abstract
Breast tumor selective antibodies (MAB) conjugated to Pseudomonas exotoxin A (PE) formed immunotoxins with potent cytotoxicities for human breast tumor cell lines. The most effective of the MAB-PE conjugates were about 500-fold more toxic to the breast tumor target cell lines than to the nontarget human fibroblast cell lines. Specificity of cytotoxicity by MAB-PE conjugates was demonstrated by protection of target cells inthe presence excess unconjugated homologous antibody. A MAB-PE conjugate inhibited protein synthesis more rapidly than the corresponding MAB-ricin toxin A chain (RTA) conjugate. Generally, there was a direct correlation between the cytotoxicity of RTA and PE when conjugated to the same MAB; MABs that made highly cytotoxic RTA conjugates made effective PE conjugates and MABs that made poorly cytotoxic RTA conjugates made PE conjugates of low cytotoxicity; however, one MAB-PE immunotoxin was cytotoxic to the human breast tumor cell lines, whereas the corresponding MAB-RTA immunotoxin was noncytotoxic at the highest dose tested. In contrast to MAB-RTA conjugates, which require a cleavable (disulfide) linkage for maximal in vitro cytotoxicity, MAB-PE conjugates were about equally cytotoxic when linked by either a cleavable or noncleavable (thioether) bond.