A human antiidiotypic
monoclonal antibody (105AD7) has been shown to induce antitumor cellular responses in animals and appears to prolong survival in patients with metastatic
colorectal cancer without associated toxicity. Proliferative leukocyte responses to the targeted
tumor antigen gp72 were observed in these patients and plasma
interleukin 2 levels were increased following immunization. Autologous
tumor tissue was not available in these patients, so antitumor cytotoxicity could not be measured. This issue has now been addressed in an adjuvant clinical study in primary
rectal cancer patients. Six patients with
rectal cancer were immunized preoperatively with 105AD7. Peripheral blood lymphocytes taken prior to immunization were tested against
tumor cells extracted from biopsies also obtained prior to immunization or from natural killer (NK)-sensitive target cells. Cryopreserved lymphocytes taken before and after
tumor immunization, fresh peripheral blood lymphocytes taken immediately prior to surgery, and lymphocytes from
tumor-draining lymph nodes were tested against autologous cells from the resected specimen or NK-sensitive target cells. Significant killing of autologous
tumor cells, which was not due to NK activity, was seen with cryopreserved lymphocytes or lymph node cells of three patients at 1-2 weeks postimmunization with 105AD7 but not on pretreatment biopsies. Enhanced NK activity was seen 2-3 weeks postimmunization in 3 of 6 patients. These results indicate that 105AD7 human
monoclonal antibody immunization enhances cytotoxicity in
rectal cancer patients by specific and nonspecific effector mechanisms.