Human-human monoclonal antibody directed against tumor surface antigen in the treatment of human malignancy. A pilot study.
Eighteen patients with a variety of refractory solid tumors received infusions of IgM class monoclonal antibody directed against tumor surface antigen and raised in a nonviral transformed human-human system. Three other patients with refractory hematologic or solid tumors had autologous marrow purged with antibody, regrown, and reinfused following high dose chemotherapy. A molecular weight of 200,000 was demonstrated for the whole antibody produced by the fusion line. Each antibody failed to react with nonspecific tumor tissue. No fetal antigen reactivity was noted. Antibody was cytotoxic. Complement dependence was not demonstrated. Chloroquine phosphate pretreatment was employed prior to each antibody infusion to block receptor recycling and host-antigen processing. Antibody dose was doubled with each treatment. Self-limiting chill and fever (with tachycardia) was noted in 12-hour infusions. Tumor biopsy following infusion demonstrated good binding for as long as 48 hours after dosing. Tumor regression was noted during infusions. Pulmonary metastases responded rapidly following infusion. Maximal shrinkage of skin metastases was noted at 4 days with some regrowth at 7 days. Reduction in size of liver metastases was the most durable response. Responses correlated with survival. There were no antibody-related deaths. Antibody used ex vivo to purge autologous bone marrow-cleared marrow of tumor. Marrow engraftment was noted between 7 and 21 days. Follow-up showed no antihuman antibody formation, alteration in renal or hepatic function, alteration in thyroid or adrenal function, or circulating antigen-antibody complexes. Natural killer cell activity and complement-activated clearing of immune complexes increased following infusion. The time for complete clearing of immune complexes from the circulation was 10 days. Mild anemia was seen after several courses of infusion. Reticulocytosis was unimpaired. Long-term follow-up showed no antihuman antibody formation or organ dysfunction.
Alonso
K
K
Laboratory Atlanta, Riverdale, Georgia 30274.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000187:drug effects / Q000378:metabolism / Q000627:therapeutic use*; D000912:Antibodies, Neoplasm / Q000187:drug effects / Q000378:metabolism / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000276:immunology*; D002738:Chloroquine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D010865:Pilot Projects; D013997:Time Factors
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; C023676:chloroquine diphosphate; D002738:Chloroquine