In vivo therapy of a murine B cell tumor (BCL1) using antibody-ricin A chain immunotoxins.

Abstract

Prolonged remissions were induced in mice bearing advanced BCL1 tumors by the combined approach of nonspecific cytoreductive therapy and administration of a tumor-reactive immunotoxin [with ricin A as the toxin component]. Thus, the vast majority of the tumor cells (.apprx. 95%) were first killed by nonspecific cytoreductive therapy using total lymphoid irradiation (TLI) and splenectomy. The residual tumor cells were then eliminated by i.v. administration of an anti-.delta. immunotoxin. In 3 of 4 experiments, all animals treated in the above fashion appeared tumor free 12-16 wk later. In 1 experiment, blood cells from the mice in remission were transferred to normal BALB/c recipients, and the latter animals have not developed detectable tumor for the 6 mo. of observation. Because 1-10 adoptively transferred BCL1 cells will cause tumor in normal BALB/c mice by 12 wk, the inability to transfer tumor to recipients might indicate that the donor animals were tumor free. In the remainder of the animals treated with the tumor-reactive immunotoxin there was a substantial remission in all animals, but the disease reappeared. All mice treated with the control immunotoxin or antibody alone relapsed significantly earlier (3-4 wk after splenectomy).