A model system involving anti-concanavalin A for antibody targeting of diphtheria toxin fragment A1.

Results obtained in a model system strongly suggest that antibodies to cell surface determinants may be used to direct the toxic potential of the A chain of diphtheria toxin (DTA). The A chain (M.W. 21,000) was covalently attached to antibody against concanavalin A (anti-Con A) by means of a disulfide-containing cross-bridge. This DTA-SS-(anti-Con A) conjugate was toxic for 3T3 cells containing Con A on their surface but was not toxic in the same concentration range for: (a) cells lacking Con A; (b) Con A-treated cells washed with buffer containing alpha-methyl-D-mannoside; (c) cells containing wheat germ agglutinin on their surface; or (d) Con A-treated mutant Chinese hamster ovary cells containing altered, toxin-insensitive elongation factor 2. Conjugates containing DTA disulfide linked to anti-wheat germ agglutinin antibody or to nonspecific rabbit immunoglobulin G were not toxic for cells coated with Con A. The results suggest a new approach to the construction of antibody-directed, tumor-specific chemotherapeutic agents. Conjugates containing DTA disulfide linked to antibody against specific cell surface antigens may also be generally useful as specific selective agents for the isolation of mutant cell lines.