In vivo follow up of the cytotoxic effect of ricin toxin vectorized by multivalent hybrid antibody on target cells

Abstract

A multivalent hybrid antibody complex composed of two IgG molecules specific for ricin toxin and two specific for the H-2 antigens of murine leukemia EL4 cells, cross-linked by SpA, was used as vector of the toxin to the target cells. The high affinity of the hybrid antibody for the specific antigens achieved an efficient attachment to the EL4 cell membrane and binding of ricin toxin; this high-molecular-weight complex, introduced by endocytosis into the leukemic cell cytoplasm, was able to specifically deliver the toxin to the target cells. The effect of multivalent hybrid antibody-vectorized toxin was followed up in vivo. This method enabled determination of the proportion of killed cells (over 90% after a single treatment of leukemic cells or about 99% after double treatment). The presence of a low proportion of tumoral cells maintaining their proliferative capacity is discussed.