Immunotoxin Conjugates Research Articles

In vivo administration of lymphocyte-specific monoclonal antibodies in nonhuman primates. Delivery of ribosome-inactivating proteins to spleen and lymph node T cells.

The selective delivery in vivo of a T lymphocyte-specific monoclonal antibody and immunotoxin conjugates to T cells in lymph node and spleen was assessed in rhesus monkeys. A transient coating of all T lymphocytes in the lymph nodes and spleens of healthy rhesus monkeys could be achieved after infusion of unconjugated anti-T11. Because derivatized antibody is cleared more rapidly than unconjugated antibody, it was necessary to infuse a higher dose of immunotoxin than antibody alone to achieve saturation of the lymphocyte binding sites with anti-T11. When sufficient antibody-toxin conjugate was infused, toxin was readily demonstrable on lymph node and spleen T cells by 16 h after infusion. This demonstration that toxins can be successfully delivered with specificity to target T cell populations in the monkey suggests that killing of restricted cell populations in vivo should be feasible.

In vivo administration of lymphocyte-specific monoclonal antibodies in nonhuman primates. In vivo stability of disulfide-linked immunotoxin conjugates.

The stability in vivo and circulatory clearance of immunotoxins were assessed in rhesus monkeys. The immunotoxins studied were T cell-specific monoclonal anti-T11 antibodies conjugated by disulfide linkage to ribosome-inactivating toxins. Intact immunotoxin was detectable in the circulation of the monkeys following a single intravenous infusion. This was demonstrated by quantitative flow-cytometric analysis, gel-filtration, and sodium dodecyl sulfate-gel electrophoresis. This intact conjugate was shown to be functional in the plasma of the infused animals in an in vitro cytotoxicity assay. However, a number of factors contributed to bring the level of circulating immunotoxin to a less than optimal level. When conjugated to a ribosome-inactivating toxin, the antibody was cleared more rapidly than was the native antibody. Furthermore, following infusion, some breakdown of the conjugate occurred, resulting in the generation of detectable levels of circulating free antibody. The present data indicate the feasibility of using immunotoxins as therapeutic tools in man.