Toxicity associated with the formation and clearance of immune complexes between antitumour monoclonal antibodies and syngeneic anti-idiotypic antibodies in mice.

We have previously shown that Balb/c mice immunised against syngeneic monoclonal antibodies (mAbs), so that they have anti-idiotypic responses against those mAbs, will clear the mAbs from the circulation as a result of immune complex formation. We report here that with three separate mAbs, this clearance of complexes can result in toxicity to the animals. This was particularly severe with one mAb (NCRC-2), in some cases leading to death. It was not seen with Fab/c or Fab fragments of NCRC-2. This toxic response could be passively transferred with serum, indicating that it was due to formation of immune complexes or to their subsequent clearance. Treatment of mice with cobra venom factor, to reduce complement levels, reduced clearance of complexes but had no effect on toxicity. The anti-histamine pyrilamine did not reduce toxicity. This is one of only a few situations in which an anti-(mouse antibody) response has been reported to be potentially dangerous, and is particularly remarkable since it occurs as a result of such a limited anti-antibody response.