Studies on Drug-Induced Immunological Tolerance.

摘要

The investigation involved the preparation of chemicals suitable for immunological screening and the immunological evaluation of these compounds. Thirteen cyclophosphamide analogs were synthesized. Following a preliminary determination of their acute toxicity,these compounds were evaluated first in sheep erythrocyte (SRBC) tolerance tests,and then in skin allograft tolerance tests. Two compounds,namely phosphoramidic mustard (NSC-69,945) and cytoxyl alcohol (NSC-52,695) were found to be especially active in inducing specific tolerance in mice in the SRBC test. Of these two compounds only one,namely cytoxyl alcohol,showed also a significant activity for the prolongation of the life of skin allografts in mice. The interesting phenomenon of the breakdown of immunological tolerance by a single injection of a suitable compound was discovered during these studies. This phenomenon,which might have important implications for cancer and viral chemotherapy,has been brought about by a mixture of phosphoramidic mustard and cytoxylamine and,to a lesser extent,by compounds NSC-72,505and NSC-72,509. (Author)